From an early stage in the development of retroviral vectors for gene therapy applications, there has been a concern that recombinant vectors could elicit cellular transformation by altering expression of either cellular proto-oncogenes or tumor suppressor genes that are proximal to the genomic integration site (Fig. 6.1). This phenomenon, referred to as insertional mutagenesis, was characterized as a property of wild type gammaretroviral viruses (previously known as murine oncoretroviral viruses) which are the prototype virus from which the recombinant vectors used in the majority of the clinical trials described in this chapter were derived (reviewed in [178]). Wild type retroviruses fall into two categories with regards to their transforming properties: Slow transforming and acute transforming retroviruses.