Although conventional gene therapy approaches typically involve the addition of anti-HIV genes to cells using semirandomly integrating viral vectors, newer and genome editing technologies based on engineered nucleases are now allowing more precise genetic modifications, the possible results of genome editing include gene disruption, which has been most notably applied to some of the coreceptor gene, or the introduction of small mutations or larger whole gene cassette insertions at a targeted locus. Genome editing has emerged recently as a more precise way to engineer cells that could also be applied to HIV/AIDS. At its heart, the technology uses advanced nucleases to introduce DNA double-strand breaks (DSBs) at a targeted locus, whose recurrent repair is exploited to achieve different outcomes. If the nonhomologous end joining (NHEJ) repair pathway is obtained, the end result can be random insertions/deletions (indels) at the break site that result in gene disruption.On the other side, more precise repair pathways based on homologous recombination can be used to copy information from an introduced DNA homology template. Such homology-directed repair (HDR) can promote a specific gene editing/mutation event or allow the site-specific addition of larger gene cassettes at the break site.