Cigarette smoking is the leading cause of death and disability in the United States (U.S.), contributing to over 440,000 deaths each year (U. S. Department of Health and Human Services [USDHHS], 2004).The selection hypothesis of smoking prevalence posits that smokers who are able to quit successfully are not burdened by specific characteristics that make it more challenging to quit (Coambs et al., 1989; Hughes, 1993; Hughes & Brandon, 2003). Notably, cigarette smoking rates and rates of cessation failure are disproportionately higher among those with elevated depressive or anxiety symptoms and disorders relative to persons with no psychiatric history, and those with many types of psychiatric conditions (Bejerot & Humble, 1999; Lasser 2000). Researchers have started to develop specialized behavioral interventions for smokers with depressive (e.g., Brown et al., 2001; Hall et al., 1998) and certain anxiety characteristics (e.g., high anxiety sensitivity; Zvolensky, Bernstein, Yartz, McLeish, & Feldner, 2008). Yet, central barriers to such work are that existing treatments for this population address only a single psychiatric comorbidity with smoking and therapeutic tactics are absent for smokers with multiple anxiety disorders or co-occurring elevated depressive and anxiety symptoms or disorders. Such neglect is unfortunate, as multiple depression and anxiety symptoms and disorders: (a) frequently co-occur in smokers (Mykletun et al., 2003), (b) are among the most common groups of psychiatric disorders (Kessler et al., 2005), (c) appear to share common (transdiagnostic) vulnerability processes implicated in the etiology of smoking (e.g., distress intolerance, anxiety sensitivity, and anhedonia; Zvolensky, Stewart, Vujanovic, Gavric, & Steeves, 2009), and (d) exhibit considerable phenomenological overlap (Mineka, Watson, & Clark, 1998). Accordingly, we are proposing a 3-year study to develop an integrated treatment for smoking cessation for anxiety-depressive vulnerable smokers. The intervention development approach will follow a staged model consistent with NIH guidelines for developing and standardizing behavioral interventions, with the proposed research representing a Stage IB study. Specifically, during the first year, startup activities will include piloting the integrated intervention on a subset of individuals (N 12), soliciting internal and external expert consultant and participant feedback, and development of the final treatment manual and procedures. The goal during this phase will be to establish feasibility of treatment delivery, participant acceptability, and potential for an effect. During te following two years, a small two-arm efficacy study (N = 60) will be undertaken comparing the new intervention to a control intervention. This study represents an important step in the larger landscape of translating basic research to more efficacious strategies for treating nicotine dependence. This study addresses an important public health issue by assessing an intervention that may lead to a more effective application for the treatment of psychiatrically at-risk smokers. The expected findings should: (1) Guide advances in the theoretical conceptualization of the mechanisms involved in anxiety-depression- smoking relations. (2) Directly inform the development of a novel and psychosocial/behavioral and pharmacological smoking cessation intervention(s) for smokers with anxiety and depressive disorders.