Simian Virus 40 (SV40) was discovered in 1959 as a covert contaminant of poliovirus vaccines prepared using Macacus monkey renal cell cultures. This inapparent polyoma virus of monkeys was detected using Cercopithecus renal cell cultures and was eliminated from poliovaccines. There has been no evidence to implicate SV40 virus of vaccine origin in long- or short-term consequences in human subjects. Of importance, SV40 virus provided a new model for basic studies of viral pathogenesis and for cell transformation and neoplasia. Neoplastic transformation is fixed on the promiscuous binding of SV40 large T antigen to anti-oncogene cellular protein elements. SV40 also served as a valuable model for defining the immunology of virus-induced cancer and in its prevention and cure. Further, it has been a prime tool for elucidating the molecular details of eukaryotic cell processes. Numerous techniques now used in molecular biology were pioneered in the SV40 system. The SV40 promoter is commonly used in vector expression constructs and it has continued to be a model to develop new tools for site-specific mutagenesis. The virus has been critically important to studies in modern genetics and in molecular biology.