Potassium (K{}^{+}) channels establish and maintain the resting potential of most living cells. Their activity is predominantly regulated by the membrane voltage or the K{}^{+} gradient across the cell membrane. However, many cells also express small-conductance calcium-activated potassium (SK) channels, which have the unique ability to translate changes in the level of the intracellular second messenger, Ca{}^{2+} to changes in the membrane K{}^{+} conductance and, therefore, the resting membrane potential. This article reviews the structure, presence, distribution, and function of SK channels, their pharmacological modulation, and their role in health and disease, emphasizing nociception and pain.