The evolutionary origin and diversification of the reptilian venom system is described. The resolution of higher-order molecular phylogenetics has clearly established that a venom system is ancestral to snakes. The diversification of the venom system within lizards is discussed, as is the role of venom delivery in the behavioural ecology of these taxa (particularly Varanus komodoensis). The more extensive diversification of the venom system in snakes is summarised, including its loss in some clades. Finally, we discuss the contentious issue of a definition for “venom”, supporting an evolutionary definition that recognises the homology of both the venom delivery systems and the toxins themselves.