As the number of mouse mutants generated by gene targeting continues to grow exponentially, the challenge is not how to generate a mutant but how to analyse the phenotype. Genes might play multiple roles in development and act in cell-autonomous and cell non-autonomous modes, making phenotypic analysis complex. Genetic mosaic analysis is a powerful tool for dissecting complex gene functions. Classical preimplantation chimeras made between mutant and wild-type embryos can answer many questions, and new genetic techniques for generating restricted genetic mosaicism promise to enhance the future power of mosaic analysis in mammals.