Genetically engineered mice have greatly improved our understanding of gene functions and disease mechanisms. Nevertheless, the traditional knock-out approach has limitations in the overall viability of mutants. The application of the Cre/loxP system in the inner ear can help bypass this difficulty by generation of conditional gene recombineering. However, to do so requires an expression system that allows ear-specific temporally inducible, gene abrogation of one or more of the increasingly available floxed genes. To date, three approaches have been successfully used to create murine inner ear-specific Cre lines: conventional transgenesis, BAC transgenesis, and gene knock-in. Unfortunately, timing of conditional Cre activity does not extend beyond the regulatory range of the gene controlling Cre expression. Rectification of this problem requires the generation of tamoxifen or tetracycline inducible systems in the inner ear. Examination of integrase expression at different loci will facilitate studies on the expression of exogenous transgenes. These genetic applications for the mouse genome will dramatically advance in vivo gene function studies.