Host cell reactivation measures the in vivo restoration of biological activity to in vitro-damaged DNA. The ability of UV-damaged viruses to replicate in infected cells hinges on the genetic makeup of the host cells. The use of damaged phage or plasmid DNA provides certain advantages over direct treatment of cells with a DNA-damaging agent in studying the cellular DNA repair mechanism. In this assay the physiology of the cell is not perturbed by the DNA-damaging treatment and, as a consequence, the fate of the transfecting DNA is solely dependent on the capacity of the host cell to process DNA damage. Most viruses use host cell proteins to repair and replicate. Taking advantage of this, a repair assay was designed to use the ability of UV-damaged viruses or plasmids to replicate in host cells as an indicator of the host repair capacity. This forms the basis for the host replication-dependent Host Cell Reactivation assay (83–88). More recently, the chloramphenicol acetyltransferase assay, originally developed to study transcriptional control in mammalian cells, was adapted to study DNA repair and mutagenesis. Instead of viruses, a UV-damaged vector DNA carrying a gene with a readily detectable phenotype is used to transfect host cells. In the absence of host repair, UV lesions block transcription, leading to reduced production of CAT and hence a reduced level of CAT activity, and vice versa. Alternatively, with an appropriate plasmid/host system, after a round of replication the plasmid is isolated from the mammalian cells and transfected into indicator bacterial cells to detect mutations.