There are marked and growing disparities in the health status among different racial/ethnic groups. Most researchers and practitioners agree health interventions that are tailored for specific populations are ethically important and more likely to succeed, yet there are few models for how to tailor interventions. This article outlines three phases and eight activities conducted to increase the cultural sensitivity of a clinical trial assessing the efficacy of bupropion for smoking cessation among African Americans. Early in the project development (Phase I) a strong partnership was built with a community-based clinic, two Advisory Boards were formed (Community and Scientific), and materials were developed. Formative research (Phase II) included a survey to assess smoking cessation needs of clinic patients and exploratory focus groups. Through pilot testing (Phase III), clinic patients tested the intervention components and, in follow-up focus groups, discussed their experiences. Over 13 months the project successfully recruited 523 African Americans into a randomized trial, and preliminary analysis suggest acceptable follow-up rates. Successful recruitment and retention suggests the activities are promising and potentially generalizable. Discussions of these activities illustrate concrete steps researchers and practitioners can take to increase the cultural sensitivity of health promotion and prevention interventions and clinical trials.