Therapeutical strategies aimed to the maximal inhibition (if not the eradication) of infection by human immunodeficiency virus should take into account the issue of the viral reservoir in the body. Recent data clearly show that latently infected lymphocytes represent a minimal part of the viral reservoir, while the majority of these cells are macrophages (variably differentiated) scattered in the tissues and lymph nodes. Immunologically-sequestred areas, such as the central nervous system, are particularly relevant in view of the different concentrations of antiviral drugs achieved in the organs. Thus, a careful analysis of the distribution of antiviral drugs, and the assessment of their activity in cells of macrophage lineage, represent key factors in the development of therapeutical strategies aimed to the "cure" of infectious patients.