Despite considerable progress in the analysis of microbial genomes, the number of validated targets suitable for the development of drugs acting on agents causing infectious diseases remains modest. The diversity of new chemical entities specific for such targets has almost not increased over the last years, while resistance to antiinfectious drugs has, in contrast, become a real threat in certain surroundings. New strategies are thus needed for selecting novel validated targets. We discuss here a combined approach which uses protein interaction mapping as the basic strategy to identify interacting domains which then serve to validate newly identified targets. The interactome of Helicobacter pylori is used as model to successively describe high-throughput protein interaction mapping, use of the H. pylori data to predict the interactome from other bacteria, analysis of interacting domains, and evaluation of the capacity of one such domain to block synthesis of flagella. The general applicability of this approach to target identification and validation, and to development of novel compounds is also discussed.