In humans, varying amounts of absorbed β‐carotene are oxidatively cleaved by the enzyme β,β‐carotene 15,15′‐monooxygenase 1 (BCMO1) into two molecules of all‐trans‐retinal. The other carotenoid cleavage enzyme β,β‐carotene 9′,10′‐dioxygenase (BCDO2) cleaves β‐carotene at the 9′,10′ double bond forming β‐apo‐10′‐carotenal and β‐ionone. Although the contribution of BCDO2 to vitamin A formation has long been debated, BCMO1 is currently considered the key enzyme for retinoid metabolism. Furthermore, BCMO1 has limited enzyme activity towards carotenoids other than provitamin A carotenoids, whereas BCDO2 exhibits a broader specificity. Both enzymes are located at different sites within the cell, with BCMO1 being a cytosolic protein and BCDO2 being located in the mitochondria. Expression of BCMO1 in tissues other than the intestine has recently revealed its function for tissue‐specific retinoid metabolism with importance in embryogenesis and lipid metabolism. On the other hand, biological activity of BCDO2 metabolites has been shown to be important in protecting against carotenoid‐induced mitochondrial dysfunction. Single‐nucleotide polymorphisms (SNPs) such as R267S and A379V in BCMO1 can partly explain inter‐individual variations observed in carotenoid metabolism. Advancing knowledge about the physiological role of these two enzymes will contribute to understanding the importance of carotenoids in health and disease.