We discuss the potential use of inhibitors of Kv1.3 potassium channels in T lymphocytes as therapeutics for multiple sclerosis. Current treatment strategies target the immune system in a non-selective manner. The resulting general immunosuppression, toxic side-effects and increased risk of opportunistic infections create the need for more selective therapeutics. Autoreactive effector-memory T (T(EM)) cells, considered to be major mediators of autoimmunity, express large numbers of Kv1.3 channels. Selective blockers of Kv1.3 inhibit calcium signaling, cytokine production and proliferation of T(EM) cells in vitro, and T(EM) cell-motility in vivo. Kv1.3 blockers ameliorate disease in animal models of multiple sclerosis, rheumatoid arthritis, type 1 diabetes mellitus and contact dermatitis without compromising the protective immune response to acute infections. Kv1.3 blockers have a good safety profile in rodents and primates.