In this study, we explored Latinx adolescents' knowledge and perceptions of biobehavioral research and their willingness to participate in such studies. We conducted four focus groups in the summer of 2014 with Latinx adolescents in Texas between the ages of 12 and 17 years (n = 17; 53% male; M [subscript age] = 14.6 years [SD = 1.66]) who were recruited from a community-based clinic. Five themes emerged from our content analysis: (a) protection of human subjects is important to participants, (b) comfort with providing different types of biological data varies depending on different factors, (c) engagement in biobehavioral research should be grounded in a cultural lens, (d) providing bilingual research staff is essential, and (e) adolescents have various motivations for participating. Findings highlighted how various factors could serve as both barriers and facilitators to participation. Our study provides insight into strategies for conducting biobehavioral research with Latinxs, who are the fastest growing group of adolescents in the United States and experience disparities in health-risk behaviors that can be better understood through research approaches that integrate biological and psychological measures. Without considering the perspectives of historically marginalized or understudied populations, we jeopardize the quality and validity of research findings, and risk harming participants.