This journal article describes methods used to recruit and retain a sample of 200 homeless youth for a four-session substance use and sexual risk reduction program at two drop-in centers in Los Angeles. Using unconventional methods, the researchers retained 91 percent of the full sample at a three-month follow-up assessment with 79 percent of the participants attending multiple sessions. The authors found that using structured materials with a small, dedicated staff helped to reach a higher retention rate with this at-risk population. This article describes the challenges researchers encounter when conducting intervention studies with homeless youth due to substance abuse, mental health problems, wariness of authority figures, and frequent relocations. It is especially challenging to retain this population across multiple program sessions and to relocate them for subsequent follow-up assessments. These retention issues can jeopardize a study’s data and conclusions.