The article discusses the critical issue of patient adherence to recommended treatment regimens, emphasizing its significant impact on health outcomes and economic burden. It highlights that patient nonadherence can lead to poor health outcomes and substantial financial costs, with estimates suggesting that nonadherence costs the US healthcare system hundreds of billions of dollars annually. The authors review decades of research, identifying key factors that influence patient adherence, including patients' knowledge and understanding of their regimen, effective communication between healthcare providers and patients, and the development of trust in the therapeutic relationship. They also emphasize the importance of patient involvement and participatory decision-making, as well as the role of patients' attitudes, beliefs, and social supports in adherence. The article further explores the impact of depression on adherence, noting that depression is a strong predictor of nonadherence. Finally, it suggests that successful interventions to improve adherence require a tailored approach, considering the unique characteristics of patients, disease conditions, and treatment regimens, and fostering a strong physician-patient partnership.The article discusses the critical issue of patient adherence to recommended treatment regimens, emphasizing its significant impact on health outcomes and economic burden. It highlights that patient nonadherence can lead to poor health outcomes and substantial financial costs, with estimates suggesting that nonadherence costs the US healthcare system hundreds of billions of dollars annually. The authors review decades of research, identifying key factors that influence patient adherence, including patients' knowledge and understanding of their regimen, effective communication between healthcare providers and patients, and the development of trust in the therapeutic relationship. They also emphasize the importance of patient involvement and participatory decision-making, as well as the role of patients' attitudes, beliefs, and social supports in adherence. The article further explores the impact of depression on adherence, noting that depression is a strong predictor of nonadherence. Finally, it suggests that successful interventions to improve adherence require a tailored approach, considering the unique characteristics of patients, disease conditions, and treatment regimens, and fostering a strong physician-patient partnership.