Selective oxidations of readily available organic molecules can lead directly to high-value chiral compounds. Although modern chemical catalysts have significantly been improved toward the selective hydroxylation of nonactivated CH bonds, cytochrome P450 monooxygenases still remain unsurpassed in their regio-, chemo-, and stereoselectivity. The exploitation of new P450 enzymes discovered through genome mining provides sought-after fine chemicals, drugs, drug metabolites, and vitamins and has already been proven superior to classical chemical synthesis in many cases. Here, we provide examples for highly selective oxidations achieved through the exploitation of naturally occurring (wild-type) P450 monooxygenases. We summarize recent achievements in the area of P450 biocatalysis and present examples for applications of P450s in industrial synthetic chemistry.