Induced chromosomal and gene mutations cause genetic diseases, birth defects and other disease conditions and play a role in carcinogenesis. While it is widely accepted that in vivo mutation assays are more relevant to the human condition than in vitro assays, our ability to evaluate mutagenesis in vivo in a broad range of tissues has historically been quite limited. The development of transgenic rodent (TGR) mutation models has given us the ability to detect, quantify and sequence mutations in a range of somatic and germ cells. This document provides a comprehensive review of the TGR mutation assay literature and assesses the potential use of these assays in a regulatory context.