This review provides a detailed perspective on epidemiologic studies of primary brain tumors to encourage multidisciplinary etiologic and prognostic studies among surgeons, neuro-oncologists, epidemiologists, and molecular scientists. Molecular tumor markers that predict survival and treatment response are being identified with hope of even greater gains in this area from emerging array technologies. Studies of inherited susceptibility and constitutive polymorphisms in genes pertinent to carcinogenesis (for example, DNA repair and detoxification genes and mutagen sensitivity) have revealed provocative findings. Inverse associations of the history of allergies with glioma risk observed in 3 large studies and reports of inverse associations of glioma with common infections suggest a possible role of immune factors in glioma genesis or progression. Studies continue to suggest that brain tumors might result from workplace, dietary, and other personal and residential exposures, but studies of cell phone use and power frequency electromagnetic fields have found little to support a causal connection with brain tumors; caveats remain. The only proven causes of brain tumors (that is, rare hereditary syndromes, therapeutic radiation, and immune suppression giving rise to brain lymphomas) account for a small proportion of cases. Progress in understanding primary brain tumors might result from studies of well-defined histologic and molecular tumor types incorporating assessment of potentially relevant information on subject susceptibility and environmental and noninherited endogenous factors (viruses, radiation, and carcinogenic or protective chemical exposures through diet, workplace, oxidative metabolism, or other sources). Such studies will require the cooperation of researchers from many disciplines. Primary malignant or benign brain tumors were estimated to be newly diagnosed in about 35,519 Americans in 2001. Epidemiologic studies enhance our understanding of this heterogeneous group of diseases in 2 ways. Descriptive studies characterize the incidence of brain tumors and the mortality and survival rates associated with them with respect to histologic tumor type and demographic characteristics of patients affected, such as their age, sex, and geographic region. Analytic epidemiologic studies either compare the risk of brain tumors in people with and without certain characteristics (cohort studies) or compare the histories of people with and without brain tumors (case-control studies) to provide information on a wide range of possible risk factors, including diet, smoking, alcohol, occupation and industry, exposure to ionizing or nonionizing radiation, infections, allergies, head trauma, family history, and inherited polymorphisms in genes related to carcinogen metabolism, oxidative metabolism, and DNA repair. Because of the relative rarity of brain tumors, most of the analytic studies are case-control studies. There is intensifying interest in understanding the causes of brain tumors because the prognosis for patients with glioblastoma and other tumor types remains grim and because dramatic progress in the molecular classification of tumors has led to the possibility of identifying etiologically homogeneous subsets of tumors. Moreover, the rapidly increasing characterization of potentially relevant genes has created an opportunity to determine which genes might make a person susceptible orThis review provides a detailed perspective on epidemiologic studies of primary brain tumors to encourage multidisciplinary etiologic and prognostic studies among surgeons, neuro-oncologists, epidemiologists, and molecular scientists. Molecular tumor markers that predict survival and treatment response are being identified with hope of even greater gains in this area from emerging array technologies. Studies of inherited susceptibility and constitutive polymorphisms in genes pertinent to carcinogenesis (for example, DNA repair and detoxification genes and mutagen sensitivity) have revealed provocative findings. Inverse associations of the history of allergies with glioma risk observed in 3 large studies and reports of inverse associations of glioma with common infections suggest a possible role of immune factors in glioma genesis or progression. Studies continue to suggest that brain tumors might result from workplace, dietary, and other personal and residential exposures, but studies of cell phone use and power frequency electromagnetic fields have found little to support a causal connection with brain tumors; caveats remain. The only proven causes of brain tumors (that is, rare hereditary syndromes, therapeutic radiation, and immune suppression giving rise to brain lymphomas) account for a small proportion of cases. Progress in understanding primary brain tumors might result from studies of well-defined histologic and molecular tumor types incorporating assessment of potentially relevant information on subject susceptibility and environmental and noninherited endogenous factors (viruses, radiation, and carcinogenic or protective chemical exposures through diet, workplace, oxidative metabolism, or other sources). Such studies will require the cooperation of researchers from many disciplines. Primary malignant or benign brain tumors were estimated to be newly diagnosed in about 35,519 Americans in 2001. Epidemiologic studies enhance our understanding of this heterogeneous group of diseases in 2 ways. Descriptive studies characterize the incidence of brain tumors and the mortality and survival rates associated with them with respect to histologic tumor type and demographic characteristics of patients affected, such as their age, sex, and geographic region. Analytic epidemiologic studies either compare the risk of brain tumors in people with and without certain characteristics (cohort studies) or compare the histories of people with and without brain tumors (case-control studies) to provide information on a wide range of possible risk factors, including diet, smoking, alcohol, occupation and industry, exposure to ionizing or nonionizing radiation, infections, allergies, head trauma, family history, and inherited polymorphisms in genes related to carcinogen metabolism, oxidative metabolism, and DNA repair. Because of the relative rarity of brain tumors, most of the analytic studies are case-control studies. There is intensifying interest in understanding the causes of brain tumors because the prognosis for patients with glioblastoma and other tumor types remains grim and because dramatic progress in the molecular classification of tumors has led to the possibility of identifying etiologically homogeneous subsets of tumors. Moreover, the rapidly increasing characterization of potentially relevant genes has created an opportunity to determine which genes might make a person susceptible or