Longitudinal studies can be hampered by poor follow-up rates, seriously reducing generalizability of the findings. Understanding the barriers, as well as approaches to overcome and adapt to these impediments, resulted in a 96.6% 18 month follow-up rate of 479 drug abusers enrolled in an NIDA funded demonstration project aimed at reducing HIV transmission among St. Louis' most vulnerable drug-using population. In this paper, we discuss the importance of phone and systems tracking, creative team work and persistence and procedures for tracking out-of-treatment drug-users by analyzing the efforts needed to reach the study subjects. We also compared the characteristics of hard-to-reach respondents with those who were less difficult. The results revealed that employment status was the only characteristic associated with being hard-to-reach. Gender, race, age, education and psychiatric status did not discriminate recruitment difficulty in this sample. The study findings suggest that although unemployment predicted recruitment difficulty, and that the locator information provided by the respondent can be very helpful, a comprehensive tracking strategy as well as persistence and creative team work are the most important determinants of the rate of success of a follow-up investigation.