Oxygenases are common tailoring enzymes involved in the biosynthesis of aromatic polyketides, they are critical determinants of the final structure of aromatic polyketides. Here we review the structures and functions of several classes of oxygenases found in the biosynthetic gene clusters of aromatic polyketides. We used the oxygenases (JadFGH) in jadomycin biosynthesis as examples to elucidate the complex roles these oxygenases play and discussed the future prospects of using oxygenases in combinatorial biosynthesis.