Small-conductance Ca²⁺-activated K⁺ channels (SK channels) are widely expressed throughout the central nervous system. These channels are activated solely by increases in intracellular Ca²⁺. SK channels are stable macromolecular complexes of the ion pore–forming subunits with calmodulin, which serves as the intrinsic Ca²⁺ gating subunit, as well as with protein kinase CK2 and protein phosphatase 2A, which modulate Ca²⁺ sensitivity. Well-known for their roles in regulating somatic excitability in central neurons, SK channels are also expressed in the postsynaptic membrane of glutamatergic synapses, where their activation and regulated trafficking modulate synaptic transmission and the induction and expression of synaptic plasticity, thereby affecting learning and memory. In this review we discuss the molecular and functional properties of SK channels and their physiological roles in central neurons.