Cytochromes P450 (P450s or CYPs) constitute a superfamily of heme-containing monooxygenases and have been shown to play a major role in both xenobiotic and endogenous metabolism. Thanks to the Human Genome Project, the current list of human CYPs should be exhaustive and so far 57 P450 encoding genes have been identified. To date, fif-teen of them, generally called “orphans” cytochromes P450, which were mainly identified by homology research between the sequences of known P450s and genomic sequences or ESTs (Expressed Sequence Tags) databases, are not fully char-acterized. However, tissue distribution, catalytic properties and physiological functions of these “novel P450s” are being analysed and partial results are already available for some of them, including CYP2 (CYP2A13, CYP2R1, CYP2S1, CYP2U1 and CYP2W1), CYP3 (CYP3A43) and CYP4 (CYP4A22, CYP4F12, CYP4F22, CYP4V2, CYP4X1, CYP4Z1) family members. In this review, we present some of the current data characterizing these P450s and discuss their potential involvement in xenobiotic toxicity and carcinogenesis, as well as their physiological relevance in pathology susceptibility.