Are the unstable residential and personal lives of homeless mentally ill (HMI) individuals so difficult as to preclude their inclusion in rigorous, longitudinal research protocols? The continued presence of HMI individuals in U.S. society has prompted the mental health research community to reconsider the question of whether clinical trial and demonstration research protocols are feasible with this population. This article briefly examines the existing research literature on recruitment and retention rates in recent studies of this population and, in more detail, the specific strategies used by researchers to recruit and retain HMI individuals as research participants. In general, with sufficient resources and the persistent use of existing strategies for recruitment and retention, HMI individuals can be successfully studied over time. Finally, to demonstrate this potential, the recruitment and retention strategies of the San Diego McKinney Homeless Mentally Ill Demonstration Research Program are described.