When I started my work at the Institute for Genetics in Cologne in 1964, I was the only immunologist among ambitious young molecular biologists. They used mutagenesis in bacteria and bacteriophages to understand biological processes, while I studied antibody responses and immunological tolerance to hapten-carrier conjugates in rabbits. Although, this led to a first model of T cell-B cell collaboration, it was frustratingly clear that ultimately immunological problems would have to be resolved by methods of molecular genetics. Twenty five years later immunology had become one of our Institute's major research areas in molecular biology. Developing conditional gene targeting in mice to study immune regulation along the lines of the work of the young molecular biologists at the time, a dream had come true. In this essay, I present this story which represents the slightly modified text of a five-minute speech given in acceptance of the Novartis Prize for basic immunology in August 2007 in Rio de Janeiro. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.