Depression, whether conceptualized as a trait, symptom, or as a diagnosable disorder, is overrepresented among smokers. Depressed smokers appear to experience more withdrawal symptoms on quitting, are less likely to be successful at quitting, and are more likely to relapse. This article documents these relationships and explores several potential links between smoking and depression. The potential efficacy of antidepressant therapy, cognitive-behavioral therapy, and nicotine replacement therapy for smokers with depressive disorders or traits is discussed. Clinical implications and the role of patient treatment matching are also discussed.