This report describes key developments in 2019–2020, identifies challenges and opportunities (including those associated with the COVID-19 pandemic) and outlines priorities for the years ahead.As a result of variable progress in priority countries, lower performance overall in 2016, and the suspension of voluntary medical male circumcision (VMMC) services during COVID-19 shutdowns, goals for VMMC coverage will be among the HIV prevention targets that will not be met in 2020, according to the fourth annual progress report of the Global HIV Prevention Coalition. The report reviews progress toward HIV prevention targets in 28 focus countries.