Mortality and morbidity rates remain high in patients with heart failure despite advances in medical therapy. Heart failure can also significantly worsen quality of life. Attention has been paid to evaluating the effects of psychological disease in patients with heart failure. Depression rates are higher in patients with heart failure than in the general population. Depression has been associated with worse outcomes in patients with heart failure. Those at highest risk for depression include patients with implantable cardioverter-defibrillators, alcohol abuse, history of depression, and multiple comorbidities. Depression may be underdiagnosed in the heart failure population, as symptoms can often be similar in the two disease states. Evidence is limited on the effects of pharmacologic and nonpharmacologic therapy for depression, specifically in patients with heart failure. Based on the available literature, patients with heart failure should be screened routinely for depression. Treatment is known to improve quality of life, but its effect on outcomes such as mortality and hospital admissions for heart failure remains unknown. If treatment includes pharmacologic strategies, selective serotonin reuptake inhibitors (especially paroxetine and sertraline), mirtazapine, and nefazodone have the strongest efficacy evidence in this population. Based on safety data of these agents and after consideration of comorbid conditions and the potential for drug interactions, a selective serotonin reuptake inhibitor should be used as first-line therapy. Finally, clinicians should not avoid beta-blockers in those with a diagnosis of depression, as recent evidence demonstrates that these agents are not associated with inducing or worsening depressive symptoms.