Depressive and insomnia symptoms are common challenges faced by individuals with chronic disease conditions. Delving into relevant literature, this chapter will explore the prevalence of insomnia and depression in individuals with chronic medical conditions as well as associations between the presence of insomnia/depressive disorders and incident chronic medical conditions. Given their high prevalence and high level of comorbidity with psychiatric complaints, we will focus on cardiovascular disease, cancer, and Alzheimer’s disease specifically. Finally, we will offer comprehensive considerations for both intervention and assessment and conclude with a clinical vignette.