Complementing mutant embryos or embryonic stem cells with normal cells in embryonic chimeras is a valuable tool for investigating phenotypes. Chimera approaches provide a method to examine the phenotype of mutant cells, including hematopoiesis, in mutants with early embryonic lethality. Complementation with normal cells in a chimera can, in most instances, rescue mutant cells to later stages of gestation and beyond, permitting analysis of contribution and function of mutant cells in various organs, both within the chimera, but also by using functional transplantation assays for hematopoietic stem and progenitor cells. This chapter describes principles and methods for the generation of mouse chimeras, for identification and quantitative analysis of cell contribution in chimeras, and for chimeric fetal liver transplantation into adult recipients and analysis of mutant cells in the adult.