Accessory subunits are an essential feature of voltage-gated potassium (Kv) channels. They determine trafficking to the plasma membrane, surface expression, gating, permeation, and pharmacology. At least three distinct classes of accessory subunits including the KCNE family can regulate Kv channel function. KCNE genes encode integral membrane proteins with a single transmembrane domain. KCNE genes span the eukaryotic kingdom and, in mutated form, can cause acquired and congenital disease. Here we review genetic, physiological, and biophysical aspects of KCNE proteins with particular emphasis on the Caenorhabditis elegans subfamily.