We propose to study the efficacy of "Ecosystem Focused Therapy" (EFT) in post-stroke depression (PSD), a disorder that afflicts a large number of stroke victims and increases mortality, cognitive impairment, and disability for years after stroke. EFT is a new, home-delivered intervention based on our integrative model of PSD, which originated from our clinical biology and treatment studies in late-life depression. It postulates two main paths to PSD. First, stroke and stroke-repair mechanisms contribute to metabolic changes mediating PSD. Second, a "psychosocial storm" stemming both from the patient's sudden disability and the change in the patient's needs and family life add a biological burden to this cascade of depressogenic events. EFT targets the "psychosocial storm" of PSD and focuses on the reciprocal interaction between the patient's abilities and the challenges of his/her "ecosystem" (family, specialized therapists). EFT follows a structured personalization approach based on the "model of adaptive functioning", in which behavior is a function of the person's competence and the demands of the environment. Thus, EFT continuously "calibrates the environment" to the PSD patient's competence level and targets the PSD "psychosocial storm" through five integrated components: 1) It offers an action-oriented, "new perspective" about the patient's recovery. 2) It provides an "adherence enhancement structure". 3) It offers a "problem solving structure" to the patient focusing on problems, valued by the patient, and pertinent to daily function. 4) It helps the family "reengineer its goals, involvement, and plans" to accommodate the patient's disability. 5) It "coordinates care with specialized therapists" with the goal to increase patient participation in rehabilitation and social activities.