Adolescents are an important target for microbicide research, as they are disproportionately affected by sexually transmitted infections and currently are underrepresented in the microbicide research literature. Furthermore, adolescents are psychosocially and biologically different from adults, and findings from adult research cannot be assumed to apply universally to adolescents. Adolescents, to date have rarely been included in clinical trials and acceptability research for microbicides, in part because their participation requires attention to unique developmental issues, including parental consent and confidentiality. Despite these challenges, adolescents should be included in microbicide clinical research. If adolescents are ultimately expected to use microbicides, it is essential that we understand the developmental, contextual, and relationship variables that may influence use and acceptability. Accordingly, the goal of this paper was to examine the issues affecting the inclusion of adolescents in microbicide clinical research as well as review the existing adolescent-specific microbicide research, which highlights the various factors that may influence use and acceptability. It is hoped that this review can provide guidance for future work with this important, specialized population.