Psychiatry has been essentially uninterested in cigarette smoking and nicotine. However, it is the view of this author that both cigarette smoking and smoking cessation are highly relevant to the clinical psychiatrist in the care of patients and that they are potentially a source of important insights into psychopathology. To support that view, the author reviews the evidence that both major depression and depressive symptoms are associated with a high rate of cigarette smoking and that lifetime history of major depression has an adverse impact on smoking cessation. He also reviews the data available on the influence of cigarette smoking cessation on the course of major depression, the relationship between cigarette smoking and other psychiatric diagnoses, particularly schizophrenia, and the neuropharmacology that might underlie these associations. Finally, the implications of these relationships for psychiatry are discussed.