Chronic diseases account for a growing proportion of the global disease burden. Managing chronic conditions is typically lifelong and requires consistent medication adherence and engagement in care. To reduce the global burden of chronic disease, behavioral interventions are needed to improve nonadherence, especially in the context of psychiatric comorbidity. In this chapter, we first provide a framework for understanding the outcomes and the role of psychotherapy in chronic disease management, including the application to low- and middle-income countries. Next, we highlight lessons learned from the HIV epidemic and how they can be leveraged across chronic conditions, including the task sharing models for adherence support. We provide an example of implementing an evidence-based psychotherapy for adherence for HIV/AIDS in South Africa using a task sharing model that is applicable across other chronic diseases. Finally, we end this chapter with future directions, including the role of technology to support adherence across chronic conditions.