OBJECTIVE To review current knowledge and the role of integrase inhibitors in the setting of HIV salvage therapy. We will discuss results from recent studies and literature and comment on the potential for integrase inhibitors in defined clinical settings. RESULTS Raltegravir has been studied most intensively in treatment-experienced patients and is the first integrase inhibitor that has been licensed for use in this patient group. Most studies have shown good tolerability data and very potent virus suppression. In patients with limited treatment options, switching from enfuvirtide appears to be well tolerated, whereas switching from a protease inhibitor-based regimen may increase the rates of viral failure. Elvitegravir also showed good results in early phase clinical trials and is currently undergoing phase III clinical trials. CONCLUSIONS Given that integrase inhibitors belong to a new class of antiretroviral agents with a diverse drug resistance profile, and are active against both chemokine (C-C motif) receptor 5 and chemokine (C-X-C motif) receptor 4 strains, they are exciting additions to salvage therapy regimen. Raltegravir and elvitegravir are metabolized via different pathways, which will affect their respective use. The major limitation for the use of integrase inhibitors is a potentially low threshold for viral drug resistance, so functional monotherapy must be avoided.