Psychosocial factors are bi-directionally associated with the pathophysiology, symptoms, and prognosis observed in heart failure. Cardiac symptom severity is both dependent on psychological appraisal processes and causally related to feelings of exhaustion and distress. Distress and depression have been shown to affect physiological processes involved in the pathogenesis and course of chronic heart failure as well as illness behaviors. Conversely, physiological consequences of heart failure such as inflammatory activation may lead to sickness behavior and depression. However, there are some indications that the secretion of natriuretic peptides observed in response to cardiac overload may also have beneficial psychological effects (e.g., anxiolysis). Quality of life is typically reduced in heart failure but functional impairment and psychological maladjustment seem to be more important for quality of life than cardiac severity markers such as systolic or diastolic function per se. Current guidelines therefore recommend complementing optimal medical care with good communication, the creation of a trustful physician-patient relationship, patient education and partnership building, as well as specialized mental health care in cases of severe or enduring mental disorders or inappropriate illness behavior. While the evidence for antidepressant drug treatment in heart failure appears inconclusive, behavioral treatments such as exercise and psychotherapy may be more promising in treating comorbid anxiety and depression.