Infection with the human immunodeficiency virus type 1 (HIV) results in a chronic infection that progressively cripples the host immune defenses. Dysregulation of physiological immune regulatory mechanisms is a hallmark of HIV infection. The function of both regulatory T cells (Treg) and indoleamine (2,3)-dioxygenase (IDO) is affected during HIV infection. Regulatory T cells (Treg) are a subset of T lymphocytes with suppressive activity, which prevent uncontrolled immune reactions and autoimmunity. IDO is an enzyme which catabolizes the essential amino acid tryptophan into bioproducts of the kynurenine pathway and has immune suppressive activity. IDO and Treg are closely connected in physiologic and pathologic conditions, in that Treg can induce IDO expression in antigen-presenting cells and IDO activity can result in the generation of Treg. Our worked has focused on Treg survival and tissue dynamics, as well as increased IDO activity in blood and lymphoid tissues during HIV infection. It will be discussed how Treg and IDO function is affected by HIV, how alterations of these immune regulatory mechanisms may favor HIV replication by dampening cell-mediated immune responses and what therapeutic interventions may be considered in order to improve anti-viral immune response.