Cyclic nucleotide-gated (CNG) channels are ion channels which are activated by the binding of cGMP or cAMP. The channels are important cellular switches which transduce changes in intracellular concentrations of cyclic nucleotides into changes of the membrane potential and the Ca2+ concentration. CNG channels play a central role in the signal transduction pathways of vision and olfaction. Structurally, the channels belong to the superfamily of pore-loop cation channels. They share a common domain structure with hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and Eag-like K+ channels. In this chapter, we give an overview on the molecular properties of CNG channels and describe the signal transduction pathways these channels are involved in. We will also summarize recent insights into the physiological and pathophysiological role of CNG channel proteins that have emerged from the analysis of CNG channel-deficient mouse models and human channelopathies.