AbstractMitochondrial potassium channels are believed to contribute to cytoprotection of injured cardiac and neuronal tissues. The following potassium channels have been described in the inner mitochondrial membrane: the ATP‐regulated potassium channel, the large conductance Ca2+‐activated potassium channel, the voltage‐gated Kv1.3 potassium channel, and the twin‐pore domain TASK‐3 potassium channel. The putative functional roles of these channels include changes in mitochondrial matrix volume, mitochondrial respiration, and membrane potential. In addition, the activity of these channels modulates the generation of reactive oxygen species by mitochondria. In this article, we discuss recent observations on three fundamental issues concerning mitochondrial potassium channels: (i) their molecular identity, (ii) their interaction with potassium channel openers and inhibitors, and (iii) their functional properties. © 2009 IUBMB IUBMB Life, 61(2): 134–143, 2009