There is a growing population of adults with congenital heart disease (CHD) due to improved survival beyond childhood. It has been suggested that adults with CHD may be at increased risk for mental health problems, particularly depression. The reported incidence of depression in CHD varies from 9% to 30%. This review examines the evidence for a higher depression rate in CHD vs general population. Possible explanations are offered from a variety of disease models, ranging from brain injury to the psychoanalytical approach. Risk factors for an abnormal emotional adjustment and depression include early exposure to stress from illness and medical interventions in infancy, separation from the parents during hospitalizations and brain organic syndromes. Later in life, patients often have to cope with physical limitations. Recent improvements in care may be protective. Current patients may benefit from an earlier age at first surgical intervention, fewer reoperations and inclusion to the mainstream schooling, among other factors. At this point, there is little systematic knowledge about evidence-based therapeutic interventions for depression in adults with CHD. Health care providers of patients with CHD should be aware of mental health challenges and may take a more proactive approach to identifying patients at risk for depression.