The voltage-gated Kv1.3 channel and the Ca 2+-activated IKCa1 K + channel are expressed in T cells in a distinct pattern that depends on the state of lymphocyte activation and differentiation. The channel phenotype changes during the progression from the resting to the activated cell state and from naı̈ve to effector memory cells, affording promise for specific immunomodulatory actions of K + channel blockers. In this article, we review the functional roles of these channels in both naı̈ve cells and memory cells, describe the development of selective inhibitors of Kv1.3 and IKCa1 channels, and provide a rationale for the potential therapeutic use of these inhibitors in immunological disorders.