A majority of P450 structures with substrate bound leave open two fundamental questions: how do substrates access and products exit the active site, given that most of the structures show a tightly closed active site, and how are protons delivered to the iron-linked dioxygen intermediate required for heterolytic cleavage of the oxygen O-O bond? These two questions highlight the requirement that P450s must undergo significant conformational dynamics to facilitate catalysis. Not too surprisingly, most detailed understanding of conformational dynamics derives from work on P450cam. A combination of crystallographic and computational studies have shown that P450cam fluctuates between three major conformational states, which are controlled by redox partner binding and an allosteric substrate-binding site far from the active site. This complexity prompts the question: Are these intricate dynamics unique to P450cam? While the structural details of substrate- and redox partner- mediated conformational dynamics are increasingly clear, the reason for this complexity remains elusive. Addressing these questions necessitates tackling an even greater challenge: understanding the biological basis/requirements and evolutionary drivers for such sophisticated control for a seemingly simple oxidation reaction.