Depression is significant among patients with arthritis and musculoskeletal illnesses. However, the impact of depression on osteoarthritis has not been extensively studied. This article highlights the close links between these 2 prevalent chronic conditions, and the associated individual and societal burden. Results from a large clinical trial of depressed older patients with arthritis showed that a focused, collaborative depression care intervention not only decreased depression but also improved arthritis-associated outcomes, such as pain severity and arthritis-related limitations in daily activities. Relative to patients given usual care, patients receiving intervention also reported better health status and higher quality of life. Analyses of the depression interventions uncovered a reciprocal interrelation between depression and pain. Higher severity of either depression or pain decreased the benefits of systematic depression treatment and was associated with worse pain and depression outcomes. Current approaches to management of depression and arthritis do not reflect readily-available evidence-based treatment. A pilot study using a combined approach to address both depression and pain problems among elderly patients with depression and osteoarthritis suggested that benefits for depression, pain, and functional outcomes are strengthened by providing both pain and depression care management. An integrated depression and pain program using evidenced-based pharmacologic and nonpharmacologic treatments is needed to achieve optimal depression and pain outcomes. Currently, a randomized trial is under way to evaluate effectiveness of a combined pain and depression intervention using pharmacologic and nonpharmacologic therapies. Key intervention components in these 2 innovative and integrated depression and pain programs can guide clinicians to treat both depression and pain with more focus and intensity.