Helper T cells are required for the initiation and maintenance of adaptive immune responses. The duration and quality of T cell responses must be tightly controlled to prevent excessive or inappropriate immune activation, a function primarily mediated by the expression of inhibitory receptors. Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) are inhibitory receptors expressed by T cells that can deliver negative signals and suppress T cell function. CTLA-4 and PD-1 are induced upon T cell activation and their expression is tightly regulated to ensure appropriate T cell responses. Here, we review the mechanisms that regulate CTLA-4 and PD-1 expression and discuss the role of these inhibitory pathways in the control of T cell responses and immune homeostasis.