At the 2025 Conference on Retroviruses and Opportunistic Infections (CROI), investigators presented updates on the global HIV epidemic. Although new HIV infections have been declining globally, new infections are expanding in Eastern Europe and central Asia, the Middle East and North Africa, and Latin America. HIV incidence remains high among key populations and their partners. Initiation of oral preexposure prophylaxis (PrEP) is increasing globally, with 91% of PrEP starts funded by the US President's Emergency Plan for AIDS Relief, and large rises in new HIV infections are predicted to occur due to international funding cuts. Several presentations focused on strategies to increase HIV testing, including home HIV self-testing, couples HIV testing, and use of digital strategies. Substance use continues to be a driver of new HIV infections. Implementation of harm reduction and opiate agonist therapy significantly reduced new infections among people who inject drugs in Malaysia, and other person-centered approaches tailored for people who use drugs are being investigated. The uptake of PrEP has been increasing in a number of priority populations; however, persistence on oral PrEP remains sub-optimal. Although the use of long-acting injectable cabotegravir (CAB-LA) remains low in the US, several programs have demonstrated high persistence. When provided choice, many individuals choose CAB-LA over other available options, and adherence to follow-up injections has been high. Several interventions to increase PrEP uptake and adherence show promise, including pharmacy-based refills and incentives, point-of-care urine tenofovir testing with counseling, and use of mobile health tools. PrEP with emtricitabine/tenofovir alafenamide was shown to reduce HIV infections in cisgender women adherent to PrEP. A single once-yearly injection with lenacapavir showed promising pharmacokinetic results and a phase III trial is planned. Interest in doxycycline postexposure prophylaxis is high, and real-world implementation has been associated with significant declines in bacterial sexually transmitted infections.