Over 25 million people worldwide are currently infected with the lentivirus HIV-1. Today, HIV-1 can be controlled with antiviral therapies such that the virus is undetectable in the blood. But the virus doesn’t completely disappear; it just hides in latently infected cells. To truly cure HIV-1, researchers need to vanquish these hidden viral reservoirs, and CRISPR may be the way to accomplish this tough job! Kamel Khalili’s lab at Temple University has demonstrated two potential strategies for CRISPR-HIV therapeutics - one using dCas9-SAM to activate HIV-1 transcription and destroy infected cells, the other using wild-type Cas9 to remove the HIV-1 genome from infected cells. Read on to learn how CRISPR can take on HIV-1 in vitro, and what obstacles must be overcome for clinical success.