We have conducted an evolutionary analysis of *Notch* genes of the vertebrates *Danio rerio* and *Mus musculus* to examine the expansion and diversification of the *Notch* family during vertebrate evolution. The existence of multiple *Notch* genes in vertebrate genomes suggests that the increase in Notch signaling pathways may be necessary for the additional complexity observed in the vertebrate body plan. However, orthology relationships within the vertebrate *Notch* family indicate that biological functions are not fixed within orthologous groups. Phylogenetic reconstruction of the vertebrate *Notch* family suggests that the zebrafish *notch1a* and *1b* genes resulted from a duplication occurring around the time of the teleost/mammalian divergence. There is also evidence that the mouse *Notch4* gene is the result of a rapid divergence from a *Notch3*-like gene. Investigation of the ankyrin repeat region sequences showed there to be little evidence for gene conversion events between repeat units. However, relationships between repeats 2–5 suggest that these repeats are the result of a tandem duplication of a dual repeat unit. Selective pressure on maintenance of ankyrin repeat sequences indicated by relationships between the repeats suggests that specific repeats are responsible for particular biological activities, a finding consistent with mutational studies of the *Caenorhabditis elegans* gene *glp-1*. Sequence similarities between the ankyrin repeats and the region immediately C-terminal of the repeats further suggests that this region may be involved in the modulation of ankyrin repeat function.