IL-2, IL-15, and IL-7 are cytokines that are critical for regulating lymphoid homeostasis. These cytokines stimulate similar responses from lymphocytes in vitro, but play markedly divergent roles in lymphoid biology in vivo. Their distinct physiological functions can be ascribed to distinct signaling pathways initiated by proprietary cytokine receptor chains, differential expression patterns of the cytokines or their receptor chains, and/or signals occurring in distinct physiological contexts. Recently, the discovery of a novel mechanism of cytokine signaling, trans-presentation, has provided further insights into the different ways these cytokines function. Trans-presentation also raises several novel cell biological and cellular implications concerning how cytokines support lymphoid homeostasis.