Depressive symptoms are detected in nearly half of patients with heart failure and are a risk factor for functional decline and death. The goal of the proposed research is to generate scientific evidence to help patients, caregivers, and providers make decisions about how best to manage depressive symptoms in advanced heart failure. This real-world randomized pragmatic trial is set to compare the effectiveness of two evidence-based treatment approaches: Behavioral Activation, or BA, a patient-centered psychotherapy that emphasizes engagement in enjoyable and valued personalized activities selected by the patient; and Antidepressant Medication Management. The proposed research will examine the impact of these treatments on the following outcomes that patients and caregivers have identified as most important or advantageous: depressive symptom reduction, improvement in functioning, general physical and mental health-related quality of life (HRQoL), heart failure-specific HRQoL, and caregiver burden. We will also examine the following outcomes that patients and caregivers have identified as disadvantageous: morbidity (as evidenced by frequent emergency department (ED) visits, hospital readmissions, longer hospital stays), and mortality. All patient/caregiver-centered outcomes will be longitudinally collected in order to assess the short-, intermediate-, and long-term impact on patients’ lives. The results from this research study will help patients, caregivers, and physicians decide what treatment path to follow when experiencing depressive symptoms in advanced heart failure. Furthermore, this study will include patients and other stakeholder engagement in all stages of the study, from the study design, outcomes selection, data collection and analysis, recruitment, development, intervention implementation, and dissemination of results.