The mouse is widely considered as a toolbox for modeling human diseases: mice are easy to handle and breed, there exist inbred strains, and the mouse genome sequence is available. Mutant mouse lines can be generated by different technologies, and standardized phenotyping of these mutant mouse lines produces a huge amount of valuable data. Useful resources for the scientific community are archives of mutant lines and strains as well as databases delivering information about the mouse lines and their availability. The phenotypic characterization of mutant mouse lines is the bottleneck within the pipeline from the generation via phenotyping to archiving of mutant mouse lines. Mouse clinics generate large data sets by the standardized, comprehensive phenotypic characterization of mutant mouse lines. There is a portfolio of phenotyping protocols available for a broad spectrum of disease areas that is considered as an international standard. For the investigation of human diseases like diabetes, obesity or the metabolic syndrome, metabolic tests to analyze mutant mouse lines become increasingly important. In this respect, challenge experiments have become the major focus to induce disease phenotypes in mutant mice that would remain undiscovered without the environmental challenges. These experimental setups reflect human conditions, where genetic predisposition and the environmental factors originating from different life style act together and enhance each other. © 2012 Springer Science+Business Media, LLC. All rights are reserved.