Objective: Cigarette smoking is the leading cause of preventable death in the United States. In addition, smoking rates among depressed and anxious smokers are higher than in the population at large. Furthermore, treating depressed and anxious smokers effectively is particularly challenging because of their significant negative affect, dysfunctional emotional regulation, severe withdrawal symptoms, and numerous institutional barriers to successful treatment. Previous reviews in this area have typically focused on depression or anxiety disorders, whereas this review focuses on both disorders. Method: This article presents a brief review of the literature on treating depressed and anxious smokers in smoking cessation programs. We also discuss treatment issues, challenges, and guidelines regarding effective interventions for depressed and anxious smokers who wish to stop smoking. Results: The potential benefits for better health and improved functioning are quite large. Moreover, the merit of pursuing evidence-based interventions with these comorbid populations of depressed and anxious smokers--including practical, multidisciplinary, and cost-effective smoking cessation programs--is compelling. Conclusions: A sensible time for an aggressive approach to this health promotion effort is now.