Project HEART, an acronym for Helping Enhance Adherence to Retroviral Therapy, was a prospective, controlled study to develop, implement, and evaluate a clinic-based behavioural intervention to prevent adherence failure among HIV-infected adults beginning their first highly active antiretroviral therapy (HAART) regimen (N = 227). In this paper, we describe the conceptualisation of the Project HEART adherence intervention, characteristics of the participants, and lessons learned implementing HEART in an inner-city clinic setting. A multi-component intervention, HEART combined enhanced education, reminders, adherence feedback, social support and adherence-focused problem solving in an integrated manner to address common cognitive, motivational, and social barriers to adherence. Unique components of the intervention included use of participant-identified adherence support partners and a standardized adherence barriers assessment to develop and implement individualised adherence plans. Lessons learned regarding the feasibility of using participant-identified support partners were as follows. Few participants eligible for the study had trouble identifying a support partner. Over 90% of support partners attended at least one intervention visit. Support partners were most available and amenable to participate early in the initiation of therapy. Participants' experiences as the 'supported' partner were generally positive. Though many participants faced barriers not easily addressed by this intervention (for example, housing instability), formally integrating support partners into the intervention helped to address many other common adherence barriers. Family and friends are an under-utilised resource in HIV medication adherence. Enlisting the help of support partners is a practical and economical approach to adherence counselling.