At the end of 2016, there were approximately 36.7 million people living with HIV worldwide with 1.6 million people being newly infected. In the same year, 1 million people died from HIV-related causes globally. The vast prevalence of HIV calls for an urgent need to develop and implement prevention programs aimed at reducing risk behaviors. Bronfenbrenner’s socio-ecological model provides an organizing framework to discuss HIV prevention interventions implemented at the individual, relational, community, and societal level. Historically, many interventions in the field of public health have targeted the individual level. Individual-level interventions promote behavior change by enhancing HIV knowledge, attitudes, and beliefs and by motivating the adoption of preventative behaviors. Relational-level interventions focus on behavior change by using peers, partners, or family members to encourage HIV-preventative practices. At the community-level, prevention interventions aim to reduce HIV vulnerability by changing HIV-risk behaviors within schools, workplaces, or neighborhoods. Lastly, societal interventions attempt to change policies and laws to enable HIV-preventative practices. While previous interventions implemented in each of these domains have proven to be effective, a multipronged approach to HIV prevention is needed such that it tackles the complex interplay between the individual and their social and physical environment. Ideally, a multipronged intervention strategy would consist of interventions at different levels that complement each other to synergistically reinforce risk reduction while simultaneously creating an environment that promotes behavior change. Multilevel interventions provide a promising avenue for researchers and program developers to consider all levels of influences on an individual’s behavior and design a comprehensive HIV risk-reduction program.