This article reviews recruitment and retention issues in a multisite, multistate (California, New York, Connecticut, Georgia, Alabama) 6-month prospective cross-sectional study focused on quality of life among 230 women with lung cancer. Recruitment of women into clinical trials and their retention are important, yet understudied. To date, few articles have described the challenges associated with recruiting women with lung cancer to participate in clinical research. Data from this trial were used to investigate the most effective strategies for recruitment across sites, to identify the most common reasons for refusal and attrition, and to identify challenges and potential solutions to recruitment and retention issues associated with multisite clinical research studies. Strategies for recruitment included letters from physicians, posters, announcements in community support groups, and newspaper and radio advertisements. Three sites allowed the researchers to contact potential participants directly, whereas 2 sites required the potential participants to contact the researchers for further information. Enrollment included 63% of the women eligible for the study (n = 230). The most common reasons for refusal were health limitations (n = 60), lack of interest (n = 46), and inconvenience (n = 16). The most common reasons for attrition (24% of the sample) were death (n = 21) and severity of illness (n = 13). Challenges related to recruitment and retention varied by geographic location.