International efforts are underway to knock out every mouse gene and carry out comprehensive phenotyping on the resulting lines. As a step towards this goal, the authors carried out viability and fertility screening of 489 mutant lines and systematically screened for adult phenotypes in 250 of these lines. Demonstrating the importance of this approach, they describe phenotypes for many previously unpublished genes and also find many phenotypes that would not have been uncovered without systematic screening. Their findings also revealed unexpectedly high levels of haploinsufficiency and pleiotropy.