It is a quarter century since the publications of evidence for the transmissibility of drug resistance among Enterobacteria (1,48). Although it was not the beginning of plasmid research, it was that discovery that led to the great expansion of work on plasmids, their natural history, and the uses to which they can be put. By their practical importance, resistance or “R” plasmids forced themselves on the attention of microbiologists. The biochemical mechanisms of plasmid-determined resistance were investigated for their biological interest and because of the need to counteract their effects. Because drug-resistant clones can so easily be selected from large populations of bacteria, resistance genes are used to label DNA molecules, providing a practical basis for the genetic analysis of many prokaryotic and eukaryotic systems.