Much of our present understanding of immunity is rooted in mutations that disrupt the development of immune cells or their sensing, signaling, or effector function. Forward genetics, which entails the creation of mutations at random and their isolation through positional cloning, has yielded much insight into what is required for an immune response to proceed. Ultimately, a comprehensive list of essential genes would seem desirable. In pursuit of this goal, we have developed tools that permit instantaneous identification of point mutations responsible for phenotype. Our progress in identifying immunologically important genes is now limited only by the speed of at which mutagenesis can be performed and the speed at which mice can be phenotypically screened. Moreover, genes can be exonerated from participation in specific immune processes as well as implicated, and saturation can be estimated at any point in the process. For the first time, it is possible to monitor the destruction of the genome in a mammalian species while maintaining surveillance over a biological process of interest.