From a biochemical perspective, the ability to incorporate oxygen at very specific points in a substrate's structure is essential to numerous synthetic and catabolic plant pathways that involve simple alkyl and aromatic hydroxylations or more complex epoxidations, aryl migrations, decarboxylations and carbon-carbon bond cleavages. Because of the restricted substrate specificities of many cytochrome P450 monooxygenases and the chemical versatility of the entire group of P450s existing in plants, significant interest exists in defining functions for those not yet characterized, in understanding catalytic-site constraints of those in biologically important pathways and in modifying them for crop improvement and biopharmaceutical production.From genomics and structural perspectives, these goals are especially challenging since P450 gene families have duplicated and diverged to unprecedented degrees as new plant pathways have evolved for the synthesis of defence toxins and other secondary metabolites. Phylogenetic comparisons based solely on primary sequences have facilitated grouping of the many, often divergent, sequences into families and subfamilies that can be compared within and between plant species. Within these individual groupings, mapping of variations that have accumulated in different regions of P450 proteins has shown that they can have drastically different effects on enzymatic functions with some affecting substrate recognition, others affecting interactions with electron-transfer partners and others not affecting activity at all.Bringing together biochemical, molecular and structural perspectives, it is now becoming possible to provide cohesive models of many functionally characterized P450s and to extend these models to related but uncharacterized P450s. Using examples taken from the sequenced Arabidopsis thaliana and Oryza sativa genomes and some functionally characterized P450s in other plant species, this review highlights their phylogenetic relationships and predicted structural similarities and differences that are likely or not likely to affect catalytic functions. Combinations of primary and tertiary structure analyses such as these can now allow researchers to better understand the evolutionary relationships among plant P450s in secondary metabolic pathways and assign tentative functions to those not yet functionally characterized. With the number of annotated plant P450 sequences exponentially increasing as genomes for medicinally important plants are being sequenced, these dual level assessments will become increasingly important for discriminating among the P450s needing to be functionally characterized.