In bacteria and archaea, the clustered regularly interspaced short palindromic repeats (CRISPR) and associated proteins (Cas) confer adaptive immunity against exogenous DNA elements. This CRISPR-Cas system has been turned into an effective tool for editing of eukaryotic DNA genomes. Pathogenic viruses that have a double-stranded DNA (dsDNA) genome or that replicate through a dsDNA intermediate can also be targeted with this DNA editing tool. Here, we review how CRISPR-Cas was used in novel therapeutic approaches against the human immunodeficiency virus type-1 (HIV-1), focusing on approaches that aim to permanently inactivate all virus genomes or to prevent viral persistence in latent reservoirs.