There has been a considerable improvement in the media available for the culture of preimplantation mouse embryos during the 40 years since mouse embryos were first cultured and successfully transferred to uterine foster mothers. Two new media, KSOM and mMTF, are becoming more commonly used. The history of the development of these media, including recent work on KSOM and mMTF, is reviewed. A major artefact in the earlier work was the two-cell block. The causes of the two-cell block and the methods by which it has been overcome are reviewed. It is concluded that even the best available media inevitably cause imbalances in the environment in which the embryos are forced to develop, because they consist of only a small subset of the compounds present in the natural environments. As a result, the embryos must adapt to these abnormal conditions if they are to survive. The implications of these conclusions on the choice of media for specific purposes are discussed.