Combination HIV prevention interventions that integrate efficacious behavioral and biomedical strategies offer the potential to reduce new HIV infections. We overview the efficacy data for three biomedical HIV prevention approaches, namely microbicides, pre-exposure prophylaxis (PrEP), and HIV vaccination; review factors associated with differential acceptability and uptake of these methods; and suggest strategies to optimize the effectiveness and dissemination of combination HIV prevention approaches. A narrative review was conducted highlighting key efficacy data for microbicides, PrEP, and an HIV vaccination and summarizing acceptability data for each of the three biomedical HIV prevention approaches. Recommendations for the integration and dissemination of combined behavioral and biomedical HIV prevention approaches are provided. To date, microbicides and an HIV vaccination have demonstrated limited efficacy for the prevention of HIV. However, PrEP has demonstrated efficacy in reducing HIV incident infections. A diverse array of factors influences both hypothetical willingness and actual usage of each biomedical prevention method. Strategies to effectively integrate and evaluate combination HIV prevention interventions are urgently needed.