The widespread use of highly active antiretroviral therapy (HAART) has dramatically reduced HIV-associated morbidity and mortality where treatment has been made available. Very high levels of adherence to HAART are a prerequisite for a successful virological and immunological response. Low adherence increases the risk of treatment failure and disease progression. It is also likely to lead to further transmission of resistant viruses, and to have a negative impact on the cost effectiveness of HAART. Low adherence is difficult to predict, and this has two key implications for service provision. Firstly, HAART should not be withheld on the basis of assumptions about adherence. Secondly, support with adherence should be provided to all patients prescribed HAART. Our understanding of barriers to and enablers of high adherence, and the evidence base regarding effective interventions, is limited. Meta-analysis of randomized controlled trials available from the general literature suggests multiple interventions are required to maintain high adherence to chronic therapy. This document recommends a series of measures for adoption within HIV clinical care settings, based on evaluation of existing data. High adherence is a process, not a single event, and therefore adherence support must be integrated into clinical follow up. Every prescribing unit should have a written policy on provision of adherence support, and ensure that staff are appropriately trained to make delivery of such services possible.