There are 31 million adults living with HIV‐1 non‐B subtypes globally, and about 10 million are on antiretroviral therapy (ART). Global evidence to guide clinical practice on ART response in HIV‐1 non‐B subtypes remains limited. We systematically searched 11 databases for the period 1996 to 2013 for evidence. Outcomes documented included time to development of AIDS and/or death, resistance mutations, opportunistic infections, and changes in CD4 cell counts and viral load. A lack of consistent reporting of all clinical end points precluded a meta‐analysis. In sum, genetic diversity that precipitated differences in disease progression in ART‐naïve populations was minimized in ART‐experienced populations, although variability in resistance mutations persisted across non‐B subtypes. To improve the quality of patient care in global settings, recording HIV genotypes at baseline and at virologic failure with targeted non‐B subtype‐based point‐of‐care resistance assays and timely phasing out of resistance‐inducing ART regimens is recommended.