Plant cytochromes P450 (P450s) catalyze a wide variety of monooxygenation/hydroxylation reactions in primary and secondary metabolism. The number of P450 genes in plant genomes is estimated to be up to 1% of total gene annotations of each plant species. This implies that diversification within P450 gene superfamilies has led to the emergence of new metabolic pathways throughout land plant evolution. The conserved P450 families contribute to chemical defense mechanisms under terrestrial conditions and several are involved in hormone biosynthesis and catabolism. Species-specific P450 families are essential for the biosynthetic pathways of species-specialized metabolites. Future genome-wide analyses of P450 gene clusters and coexpression networks should help both in identifying the functions of many orphan P450s and in understanding the evolution of this versatile group of enzymes.