Nearly 1.3 million new HIV infections occur annually worldwide. Antiretroviral therapy given as pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) is highly effective in preventing HIV infection. PrEP options include long-acting injectable cabotegravir or daily oral medication with either tenofovir DF-emtricitabine (TDF-FTC) or tenofovir alafenamide-emtricitabine (TAF-FTC). Event-driven prevention options for infrequent exposures include on-demand dosing of oral TDF-FTC and PEP. Identifying the optimal choice for HIV prevention for an individual patient requires an understanding of types of exposures such as risk of transmission through sexual contact or injection drug use that may lead to HIV acquisition, the frequency of these exposures, access to biomedical prevention options, and individual characteristics. The use of biomedical HIV prevention can be dynamic. Since the risk of acquiring HIV may change over time, the ideal prevention intervention for each individual may also shift.