One of the critical clinical decisions made in antiretroviral therapy (ART) is when to switch from an initial regimen to another due to treatment failure. This complex process requires consideration of multiple factors including: (1) what type of monitoring (e.g. clinical, immunologic, virologic) is available to guide switching; (2) establishing criteria for treatment failure (e.g. viral load >10,000 copies/mL); (3) integrating data from different types of monitoring; (4) making a decision; and, if possible, (5) follow-up and monitoring to determine patient outcomes. The initial step in this model of deciding when to switch is determining what type of monitoring for guiding when to switch is available and appropriate. This review seeks to find and summarize evidence on optimal monitoring strategies for guiding when to switch first-line regimens due to treatment failure among adults and adolescents living with HIV in low-resource settings. This review was one of a series of reviews prepared in 2009 at the request of the World Health Organization to inform the development of new guidelines on ART for adults and adolescents.