Enzymatic reactions take place with high chemo-,regio-,and stereo-selectivity,appealing for the direct functionalization of abundant and inexpensive compounds with C-H bonds to make fine chemicals such as high-value intermediates and pharmaceuticals.This review summarizes recent progress in the enzymatic functionalization of C-H bonds with an emphasis on heme enzymes such as cytochrome P450s,chloroperoxidase and unspecific peroxygenases.Specific examples are discussed to elucidate the applications of the molecular and process engineering approaches to overcome the challenges hindering enzymatic C-H functionalization.Also discussed is the recent development of the chemo-enzymatic cascade as an effective way to integrate the power of metal catalysis and enzymatic catalysis for C-H functionalization.