The discovery of a diverse and unique set of ion channels in T lymphocytes has led to a rapidly growing body of knowledge about their functional roles in the immune system. Here we review the biophysical and molecular characterization of K⁺, Ca²⁺, and Cl⁻ channels in T lymphocytes. Potent and specific blockers, especially of K⁺ channels, have provided molecular tools to elucidate the involvement of voltage- and calcium-activated potassium channels in T-cell activation and cell-volume regulation. Their unique and differential expression makes lymphocyte K⁺ channels excellent pharmaceutical targets for modulating immune system function. This review surveys recent progress at the biophysical, molecular, and functional roles of the ion channels found in T lymphocytes.