Interleukin-2 was discovered in 1976 as a T-cell growth factor. It was the first type I cytokine cloned and the first for which a receptor component was cloned. Its importance includes its multiple actions, therapeutic potential, and lessons for receptor biology, with three components differentially combining to form high, intermediate, and low-affinity receptors. IL-2Rα and IL-2Rβ, respectively, are markers for double-negative thymocytes and regulatory T-cells versus memory cells. γc, which is shared by six cytokines, is mutated in patients with X-linked severe-combined immunodeficiency. We now cover an under-reviewed area—the regulation of genes encoding IL-2 and IL-2R components, with an effort to integrate/explain this knowledge.