Embryonic lethality is a common phenotype that occurs in mice that are homozygous for genetically engineered mutations. These phenotypes highlight the time and place that a gene is first required during embryogenesis. Early embryonic lethality (ie, before and up to mid-gestation) can be straightforward to analyze because the stage at which death occurs suggests why an embryo has failed. Here we summarize general strategies for analyzing early embryonic lethal phenotypes in genetically engineered mouse mutants.