Voltage-gated potassium (Kv) channels mediate rapid, selective diffusion of K+ ions through the plasma membrane, controlling cell excitability, secretion and signal transduction. KCNE genes encode a family of single transmembrane domain proteins called MinK-related peptides (MiRPs) that function as ancillary or beta subunits of Kv channels. When co-expressed in heterologous systems, MiRPs confer changes in Kv channel conductance, gating kinetics and pharmacology, and are fundamental to recapitulation of the properties of some native currents. Inherited mutations in KCNE genes are associated with diseases of cardiac and skeletal muscle, and the inner ear. This article reviews our current understanding of MiRPs--their functional roles, the mechanisms underlying their association with Kv alpha subunits, their patterns of native expression and emerging evidence of the potential roles of MiRPs in the brain. The ubiquity of MiRP expression and their promiscuous association with Kv alpha subunits suggest a prominent role for MiRPs in channel dependent systems.