Cytochromes P450 (CYPs) are versatile oxidase catalysts that play pivotal roles in drug metabolism. They are highly regarded as biotechnological tools for their capacity to perform regio- and stereo-selective oxidations. Human CYPs source electrons for oxygen activation from one or more separate redox partner enzymes. However, several CYP enzymes are now known in which the CYP is covalently linked to a reductase system. Some of these systems offer distinct advantages over typical CYPs as efficient, self-contained units capable of important biotransformations, including synthesis of high value chemicals and pharmaceuticals. Protein engineering has been widely applied to produce variant CYP fusions with desirable activities. The review focuses on the nature and diversity of CYP/redox partner fusion enzymes and their biocatalytic potential.