Background: Given the epidemic of lifestyle-related chronic diseases, building the evidence base for physical activity and dietary behavior change interventions with a wide population reach is of critical importance. For this purpose, telephone counseling interventions have considerable potential. Purpose: To systematically review the literature on interventions for physical activity and dietary behavior change in which a telephone was the primary method of intervention delivery, with a focus on both internal and external validity. Methods: A structured search of PubMed, Medline, and PsycInfo was conducted for studies published in English from 1965 to January 2006. Studies targeted primary or secondary prevention in adults, used randomized designs, and included physical activity and/or dietary behavior outcomes. Results: Twenty-six studies were reviewed, including 16 on physical activity, six on dietary behavior, and four on physical activity plus dietary behavior. Twenty of 26 studies reported significant behavioral improvements. Positive outcomes were reported for 69% of physical activity studies, 83% of dietary behavior studies, and 75% of studies addressing both outcomes. Factors associated with positive outcomes appear to be the length of intervention and the number of calls, with interventions lasting 6 to 12 months and those including 12 or more calls producing the most favorable outcomes. Data on the representativeness of participants, implementation of calls, and costs were reported much less frequently. Conclusions: There is now a solid evidence base supporting the efficacy of physical activity and dietary behavior change interventions in which the telephone is the primary intervention method. Thus, research studies on broader dissemination are necessary, and should address questions relevant to the translation of this body of work into population health practice.