The mammalian target of rapamycin (mTOR) signaling pathway is a critical regulator of cell growth and metabolism. Deregulation of mTOR has been implicated in various diseases, including cancer, diabetes, obesity, neurological disorders, and genetic disorders. Rapamycin, a specific mTOR inhibitor, has shown promise in treating certain diseases, but its monotherapy has limitations due to its cytostatic rather than cytotoxic effects and the presence of feedback loops that can re activate signaling pathways. Recent studies have highlighted the importance of combination therapy with rapamycin to overcome these limitations and enhance efficacy. Rapamycin has been approved for the treatment of advanced renal cancer and neuroendocrine tumors, but its broader clinical success remains limited. The mechanism of action of rapamycin involves its inhibition of mTORC1, which is crucial for cell growth and proliferation, while mTORC2, which regulates cell survival and actin/cytoskeleton organization, can also be inhibited by rapamycin over time. The effects of rapamycin on longevity and metabolism are complex, with both beneficial and detrimental outcomes depending on the duration and dosage of treatment. Future research aims to develop new strategies to overcome the limitations of monotherapy and improve the efficacy and safety of rapamycin-based treatments.The mammalian target of rapamycin (mTOR) signaling pathway is a critical regulator of cell growth and metabolism. Deregulation of mTOR has been implicated in various diseases, including cancer, diabetes, obesity, neurological disorders, and genetic disorders. Rapamycin, a specific mTOR inhibitor, has shown promise in treating certain diseases, but its monotherapy has limitations due to its cytostatic rather than cytotoxic effects and the presence of feedback loops that can re activate signaling pathways. Recent studies have highlighted the importance of combination therapy with rapamycin to overcome these limitations and enhance efficacy. Rapamycin has been approved for the treatment of advanced renal cancer and neuroendocrine tumors, but its broader clinical success remains limited. The mechanism of action of rapamycin involves its inhibition of mTORC1, which is crucial for cell growth and proliferation, while mTORC2, which regulates cell survival and actin/cytoskeleton organization, can also be inhibited by rapamycin over time. The effects of rapamycin on longevity and metabolism are complex, with both beneficial and detrimental outcomes depending on the duration and dosage of treatment. Future research aims to develop new strategies to overcome the limitations of monotherapy and improve the efficacy and safety of rapamycin-based treatments.