Numerous investigators have examined the role of negative affective states and affect regulation in the initiation and development of cigarette smoking behavior, smoking cessation, and relapse prevention. Affect regulation refers to any attempt to alleviate negative mood states by means of pharmacologic-, cognitive-, behavioral- or environmental-change methods. The psychological construct/process of affect regulation is examined in relation to (1) the initiation, development, and maintenance of the cigarette smoking habit; (2) the process of quitting smoking; and (3) the long-term maintenance of smoking abstinence versus relapse. Various psychosocial factors and physiological mechanisms are explored that have been hypothesized to be links between negative mood states, nicotine addiction, and smoking cessation. Implications for smoking cessation treatment are discussed in the areas of (1) the use of pharmacologic agents, such as clonidine, in the reduction of nicotine withdrawal symptoms; (2) nicotine replacement therapy; and (3) skills-training approaches to smoking cessation and relapse prevention.