Small conductance Ca-activated K channels (SK channels) are important determinants of neuronal excitability. SK channels are gated solely by intracellular Ca ions and are activated by increased levels of cytosolic Ca such as occur during an action potential. SK channel activity exerts a repolarizing effect that continues past the action potential spike and in many neurons contributes to a prolonged afterhyperpolarization. Structurally, SK channels are tetramers of the alpha, pore-forming subunits, together with four calmodulins (CaM). CaM binds to the intracellular C-terminus of the channel subunits. Ca binding to the N-lobe E-F hands of CaM induces channel gating. Recent studies reveal that the SK channel complex contains several additional, constitutively associated regulatory proteins. Moreover, the molecular composition of the SK channel complex may vary in distinct subcellular compartments, suggesting that the same expressed alpha subunit may serve a variety of roles depending upon subcellular address and macromolecular identity. The distinct coupling of SK channels to different Ca sources in dendrites, where they affect dendritic integration, and in spines where they modulate NMDA receptor function and impact synaptic plasticity supports this concept.