Cloning by nuclear transfer in mammals has revealed the remarkable ability of an oocyte to reprogram transferred cell nuclei and induce them to recapitulate the developmental program. This chapter summarizes the method used since 1998 for mouse cloning, which differs from that for large animal cloning. A Piezo-drill micromanipulator allows direct injection of nuclei into enucleated mice oocytes instead of the electrofusion method used for introducing a nucleus into an enucleated oocyte of a large animal. After activation, reconstructed embryos are allowed to develop to the morulae or blastocyst stage before transfer into surrogate mothers.