The discovery of a diverse and unique subset of ion channels in T lymphocytes has led to a rapidly growing body of knowledge about their functional roles in the immune system. Potent and specific blockers have provided molecular tools to probe channel structure-function relations and to elucidate the involvement of K+, Ca2+, and Cl- channels in T-cell activation and cell volume regulation. Recent advances in analyzing Kv1.3 channel structure-function relationships have defined binding sites for channel blockers, which have now been shown to be effective in suppressing T-cell function in vivo. Ion channels may provide excellent pharmaceutical targets for modulating immune system function.