Cre recombinase has become an important tool in the precise manipulation of the genome, and its adoption has led to the development of increasingly accurate mouse models for the understanding of gene function. Although much of current work exploits the alacrity and precision with which Cre catalyzes excisive DNA recombination, Cre also is adept at the insertion of heterologous DNA into the genome. The precision and efficiency with which Cre can target DNA to a predesignated locus in the genome promises to facilitate understanding of mutant genes and allelic variants in their natural chromosomal context.