Carotenoid cleavage dioxygenases (CCDs) constitute a family of enzymes that catalyze reactions of carotenoids, stilbenoids, and closely related compounds with dioxygen to achieve regioselective oxidative splitting of their alkene bonds into carbonyl-containing products. This activity is enabled by a nonheme iron cofactor found in all such enzymes that facilitates activation of dioxygen for the reaction. These enzymes coordinate iron using four primary sphere His residues and an associated set of three outer sphere Glu residues. In their resting states, the iron centers of these enzymes are in a high-spin (S = 2) Fe^II electronic configuration and contain a bound solvent molecule making them five coordinate with a distorted square pyramidal geometry. The CCD iron center is reactive toward nitric oxide in the presence or absence of organic substrate and the resulting S = 3/2 {FeNO}⁷ complex, which mimics in some respects an iron-oxy adduct, has been used to study substrate binding to the CCD active site. Crystallographic studies using cobalt-substituted CCDs have enabled structures of these enzymes in complex with stilbenoid substrates to be determined revealing the positioning of the scissile alkene bond with respect to the metal center. CCDs adopt a seven-bladed β-propeller fold with iron coordinated on the top end of the propeller axis where it is covered by an α-helical dome that constitutes a bulk of the active site structure. While the modes of iron coordination and overall structure of carotenoid- and stilbenoid-cleaving CCDs are similar, these enzymes are divergent with respect to the structure of their substrate-binding clefts and membrane-binding characteristics. CCDs are broadly distributed in nature and play important roles in diverse and numerous biologic processes ranging from production of retinal chromophores for light detection to degradation of lignin-derived stilbenes in pulping-waste sludge.