The PI3K pathway is a critical regulator of cellular metabolism and immune function, with significant implications for cancer and other diseases. This review discusses the roles of class I PI3Ks in these processes and highlights recent advances in PI3K-targeted therapies. PI3K activity is stimulated by oncogenes and growth factor receptors, and elevated signaling is a hallmark of cancer. Many PI3K pathway inhibitors have been tested in clinical trials, with some showing regulatory approval for certain cancers. However, on-target toxicities and challenges in efficacy/toxicity profiles remain. Understanding the roles of PI3K in metabolism and immune regulation is essential for developing effective therapies. The PI3K pathway is involved in various cellular processes, including cell growth, metabolism, migration, and secretion. Aberrations in PI3K signaling contribute to a wide range of diseases, including cancer, immunological disorders, and diabetes. The review also discusses the structure and activation of class I PI3K enzymes, the effects of activating mutations in cancer, and the roles of PI3K effectors in cellular processes. The PI3K pathway is crucial for immune function, with distinct roles in innate and adaptive immunity. Inflammation and immune responses are regulated by PI3K signaling, and its inhibition can have significant effects on immune cell function. The review highlights the importance of understanding PI3K signaling in the context of cancer and other diseases, and the need for targeted therapies that minimize off-target effects. The PI3K pathway is a complex network of interactions that requires careful consideration when developing therapeutic strategies.The PI3K pathway is a critical regulator of cellular metabolism and immune function, with significant implications for cancer and other diseases. This review discusses the roles of class I PI3Ks in these processes and highlights recent advances in PI3K-targeted therapies. PI3K activity is stimulated by oncogenes and growth factor receptors, and elevated signaling is a hallmark of cancer. Many PI3K pathway inhibitors have been tested in clinical trials, with some showing regulatory approval for certain cancers. However, on-target toxicities and challenges in efficacy/toxicity profiles remain. Understanding the roles of PI3K in metabolism and immune regulation is essential for developing effective therapies. The PI3K pathway is involved in various cellular processes, including cell growth, metabolism, migration, and secretion. Aberrations in PI3K signaling contribute to a wide range of diseases, including cancer, immunological disorders, and diabetes. The review also discusses the structure and activation of class I PI3K enzymes, the effects of activating mutations in cancer, and the roles of PI3K effectors in cellular processes. The PI3K pathway is crucial for immune function, with distinct roles in innate and adaptive immunity. Inflammation and immune responses are regulated by PI3K signaling, and its inhibition can have significant effects on immune cell function. The review highlights the importance of understanding PI3K signaling in the context of cancer and other diseases, and the need for targeted therapies that minimize off-target effects. The PI3K pathway is a complex network of interactions that requires careful consideration when developing therapeutic strategies.