Major depressive disorder (also known as clinical depression, major depression, unipolar depression, or unipolar disorder) is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and loss of interest or pleasure in normally enjoyable activities. The term "major depressive disorder" was selected by the American Psychiatric Association to designate this symptom cluster as a mood disorder in the 1980 version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) classification, and has become widely used since. The general term depression is often used to denote the disorder, but as it can also be used in reference to other types of psychological depression, more precise terminology is preferred for the disorder in clinical and research use. Major depression is a disabling condition which adversely affects a person's family, work or school life, sleeping and eating habits, and general health. In the United States, approximately 3.4% of people with major depression commit suicide, and up to 60% of people who commit suicide have depression or another mood disorder.

The diagnosis of major depressive disorder is based on the patient's self-reported experiences, behavior reported by relatives or friends, and a mental status exam. There is no laboratory test for major depression, although physicians generally request tests for physical conditions that may cause similar symptoms. The most common time of onset is between the ages of 30 and 40 years, with a later peak between 50 and 60 years. Major depression is reported about twice as frequently in women as in men, and women attempt suicide more often, although men are at higher risk for completing suicide.

Most patients are treated in the community with antidepressant medication and some with psychotherapy or counselling. Hospitalization may be necessary in cases with associated self-neglect or a significant risk of harm to self or others. A minority are treated with electroconvulsive therapy (ECT), under a short-acting general anaesthetic. The course of the disorder varies widely, from one episode lasting months to a lifelong disorder with recurrent major depressive episodes. Depressed individuals have shorter life expectancies than those without depression, in part because of greater susceptibility to medical illnesses and suicide. Current and former patients may be stigmatized.

The understanding of the nature and causes of depression has evolved over the centuries, though this understanding is incomplete and many aspects of depression are still the subject of discussion and research. Psychological, psycho-social, hereditary, evolutionary and biological causes have been proposed. Psychological treatments are based on theories of personality, interpersonal communication, and learning. Most biological theories focus on the monoamine chemicals serotonin, norepinephrine, and dopamine, which are naturally present in the brain and assist communication between nerve cells. Monoamines have been implicated in depression, and most antidepressants work to increase the active levels of at least one.