In his State of the Union Address on February 5, 2019, President Donald J. Trump announced his administration's goal to end the domestic HIV epidemic. Following the announcement of the Ending the HIV Epidemic: A Plan for America initiative, the president proposed $291 million in new funding for the fiscal year 2020 Department of Health and Human Services (HHS) budget to implement a new initiative to reduce the number of new HIV infections by 75% in the next five years (2025) and by 90% in the next 10 years (2030). This is in addition to the $20 billion the US government already spends each year, domestically, for HIV prevention and care.With this initiative, HHS recognizes that the time to end the HIV epidemic is now: we have the right data, the right biomedical and behavioral tools, and the right leadership. With the new resources, the goal is achievable.This article outlines how this initiative will be accomplished through the implementation of four fundamental strategies that will be tailored by local communities on the basis of their own needs and strengths.