The cytochromes P450 form an enormous family of over 20 000 enzyme variants found in all branches of life. They catalyze the O2 dependent monooxygenation of a wide range of substrates in reactions important to drug metabolism, biosynthesis and energy utilization. Understanding how they function is important for biomedical science and requires a full description of their notorious propensity for specificity and promiscuity. The bacterial P450cam is an unusual example, having the most well characterized chemical mechanism of all of the forms. It also undergoes an increasingly well characterized structural change upon substrate binding, which may be similar to to that displayed by some, but not all forms of P450. Finally, P450cam is one of the rare forms that have a strict requirement for a particular electron donor, putidaredoxin (pdx). Pdx provides the required electrons for enzyme turnover, but it also induces specific changes in the enzyme to allow enzyme turnover, long known as its effector role. This review summarizes recent crystallographic and double electron–electron resonance studies that have revealed the effects of substrate and pdx binding on the structure of P450cam. We describe an emerging idea for how pdx exerts its effector function by inducing a conformational change in the enzyme. This change then propagates to the active site to enable cleavage of the ferric–hydroperoxy bond during catalysis, and appears to provide a very elegant approach for P450cam to attain both high efficiency and protection from oxidative damage.