The growth of immigrant populations in the United States over the past 20 years has increased the need to enhance understanding about the risk factors that influence their substance abuse and HIV risk behaviors. Today, Latinos account for the largest majority of immigrants gaining entry into the United States. As the largest and fastest growing minority subgroup in the United States, they bear a disproportionate burden of disease and death compared to non-Latinos. Latinos are confronted with escalating HIV and substance-abuse problems, particularly Latinos between the ages of 18–34. This paper is based on our longitudinal study on the drug using and HIV risk behaviors of 527 recent Latino immigrants between the ages of 18–34 who have lived in the United States less than 1 year. The data collection activities of this study have provided insights in identifying, recruiting, interviewing, and retaining Latinos in community-based studies. Strategies, such as utilizing a combination of translation techniques, ensured the development and implementation of culturally appropriate questionnaires. Respondent-driven sampling facilitated identifying participants. Establishing rapport and trust was critical for interviewing, and maintaining a tracking protocol was most important for retention. The lessons learned from this study can guide substance abuse and HIV researchers when recruiting, interviewing, and retaining recent Latino immigrants in future epidemiologic studies. (Am J Addict 2011;21:11–22)