The cytochrome P450 superfamily is responsible primarily for human drug metabolism, which is of critical importance for the drug discovery and development. Rapid advancement of bioinformatics, functional genomics and metabolomics has been made over the last decade. These disciplines are essential in target identification, lead discovery and optimization. In this review, we summarize the recent progress on cytochrome P450 and its role on drug metabolism in the context of bioinformatics, functional genomics and metabolomics. Data are integrated into various databases and web-based platforms on cytochrome P450. These research tools and resources are playing an increasingly important role in drug discovery, and are helping in achieving the ultimate goal of personalized medicine, that is, to prescribe personalized drugs according to each person's genetic makeup, metabolic level, and drug disposition.