Despite the availability of 25 antiretroviral agents to treat HIV infection and the significant progresses made in the clinical pharmacology of HIV drugs, viral suppression and immune restoration remain problematic in a large number of HIV-infected persons. One of the main factors responsible for this partial therapeutic success is the difficulty patients have adhering consistently to antiretroviral therapy. Barriers to adherence are diverse and complex and evolve over time, complicating the monitoring of medication-taking behaviors. Consequently, multilevel interventions are often needed to address thoroughly adherence issues. Given the rapid and constant evolution of HIV treatments, innovative multidisciplinary programs integrating HIV pharmacotherapy specialists, as the “medication expert,” are being implemented. Because of his or her advanced knowledge of antiretrovirals, the HIV pharmacotherapy specialist is highly qualified to evaluate patients with complex regimens who are facing barriers to successful care and who need tailored interventions and long-term follow-up.