Hypoxia-inducible factor 1 (HIF-1) is a crucial protein complex that regulates cellular responses to low oxygen levels. HIF-1α, a component of HIF-1, is constitutively expressed but its activity is tightly regulated by cellular oxygen tension. Under normoxic conditions, HIF-1α is rapidly degraded through ubiquitination and proteasomal pathway. However, under hypoxic conditions, HIF-1α is stabilized and forms a heterodimer with HIF-1β, leading to the transcriptional activation of genes involved in angiogenesis, glycolysis, and other cellular processes. This review highlights the role of HIF-1 in various physiological and pathological processes, including ischemic cardiovascular disorders, cerebral ischemia, retinal ischemia, pulmonary hypertension, pregnancy disorders, and cancer. HIF-1α overexpression is common in human cancers and is associated with poor clinical outcomes. Therapeutic strategies targeting HIF-1 activity are being explored to exploit this pathway for the treatment of diseases characterized by increased hypoxia.Hypoxia-inducible factor 1 (HIF-1) is a crucial protein complex that regulates cellular responses to low oxygen levels. HIF-1α, a component of HIF-1, is constitutively expressed but its activity is tightly regulated by cellular oxygen tension. Under normoxic conditions, HIF-1α is rapidly degraded through ubiquitination and proteasomal pathway. However, under hypoxic conditions, HIF-1α is stabilized and forms a heterodimer with HIF-1β, leading to the transcriptional activation of genes involved in angiogenesis, glycolysis, and other cellular processes. This review highlights the role of HIF-1 in various physiological and pathological processes, including ischemic cardiovascular disorders, cerebral ischemia, retinal ischemia, pulmonary hypertension, pregnancy disorders, and cancer. HIF-1α overexpression is common in human cancers and is associated with poor clinical outcomes. Therapeutic strategies targeting HIF-1 activity are being explored to exploit this pathway for the treatment of diseases characterized by increased hypoxia.