Introduction: The HIV and hepatitis B virus (HBV) epidemics are interconnected with shared routes of transmission and specific antiviral drugs that are effective against both viruses. Nearly, 300 million people around the world live with chronic HBV, many of whom are from priority populations who could benefit from HIV prevention services. Oral pre-exposure prophylaxis (PrEP) for HIV has implications in the prevention and treatment of HBV infection, but many people at increased risk of HIV acquisition may instead prefer long-acting formulations of PrEP, which are currently not active against HBV. Discussion: People at increased risk for HIV acquisition may also be at risk for or already be living with HBV infection. Oral PrEP with tenofovir is effective in preventing both HIV and HBV, and tenofovir is also the recommended treatment for chronic HBV infection. Although implementation of oral PrEP has been challenging in sub-Saharan Africa, investments in its scale-up could secondarily reduce the clinical impact of HBV. Long-acting PrEP, including injectable medicines and implantable rings, may overcome some of the implementation challenges associated with oral PrEP, such as daily pill burden, adherence challenges and stigma; however, current formulations of long-acting PrEP do not have activity against HBV replication. Ideally, PrEP programmes would offer both oral and long-acting formulations with HBV screening to optimize HIV prevention services and HBV prevention and care, when appropriate. People who are not immune to HBV would benefit from being vaccinated against HBV before initiating long-acting PrEP. People who remain non-immune to HBV despite vaccination may benefit from being offered oral, tenofovir-based PrEP given its potential for HBV PrEP. People using PrEP and living with HBV who are not linked to dedicated HBV care would also benefit from laboratory monitoring at PrEP sites to ensure safety when using and after stopping tenofovir. PrEP programmes are ideal venues to offer HBV screening, HBV vaccination for people who are non-immune and treatment with tenofovir-based PrEP for people with indications for HBV therapy. Conclusions: Long-acting PrEP holds promise for reducing HIV incidence, but its implications for the HBV epidemic, particularly in sub-Saharan Africa, should not be overlooked.