Reaction mechanisms of redox-active enzymes have for a long time been challenging targets for theoretical research. In this review, a quantum chemical approach will be described which during recent years has been applied in our laboratory to a number of the most interesting of these enzymes. Hybrid density functional theory is used where full geometry optimizations are done with a medium basis and final energies are evaluated using a much larger basis. Models consisting of 40-50 atoms and which contain the active site metal complex, including only the first-shell amino acid ligands, are normally employed. The protein surrounding is treated as a homogeneous dielectric medium. Results demonstrating the accuracy reached in this type of model are given, and a number of examples are described, showing the type of problems that can be treated. The most important of these are taken from studies on photosynthesis and oxidative phosphorylation (respiration).