The US overdose crisis is driving a surge in HIV diagnoses among persons who inject drugs (PWID). Innovative approaches are needed to address this increase in cases. Although HIV self-testing (HIVST) was hailed as a potential “game-changer” upon initial approval by the Food and Drug Administration over a decade ago, this convenient testing modality has not reached its full potential to impact the HIV epidemic. Nevertheless, lessons regarding self-testing for infectious diseases from the COVID-19 pandemic present an opportunity to increase HIVST uptake and reach current US goals of Ending the HIV Epidemic (EHE) by 2030. In this commentary, we first discuss facilitators and barriers of HIVST for PWID. We then explore how lessons regarding self-testing during the COVID-19 pandemic can allow us to realize the potential of HIVST for PWID. We conclude by suggesting the future utilization of HIVST to address 2 EHE pillars, rapid diagnosis of HIV cases and cluster identification.