Cigarette smoking continues to be a major public health problem. Tobacco dependence interventions, as recommended by the USPHS Clinical Practice Guideline are not effective for all smokers. A need exists for new medications to treat various aspects of tobacco dependence, such as the reinforcing effects of nicotine, relief of nicotine withdrawal symptoms and prevention of early relapse. The neurobiology of the effect of methylphenidate is similar to that of the reinforcing effects of nicotine. In a small previous study, methylphenidate was reported to improve nicotine withdrawal symptoms and short term quit rates. Methylphenidate is well tolerated, has low abuse potential, and is less expensive compared to other tobacco dependence interventions. ConcertaTM, a long acting preparation of methylphenidate, is administered once a day, has similar bioavailability as the generic drug administered 3 times a day and has an overall similar or improved efficacy compared to generic methylphenidate. We plan to obtain preliminary efficacy data in a randomized, placebo-controlled phase II study assessing the effect of methylphenidate in cigarette smokers for increasing 7-day point prevalence smoking abstinence at end of treatment and 7-day point prevalence and prolonged smoking abstinence at 6-months. Critical and systematic evaluations of newer, innovative, and well-tolerated treatments to help treat tobacco use and dependence will provide a wider choice of therapeutic agents to smokers wishing to become abstinent from tobacco use.