Cytoplasmic control of preimplantation development is not a 'new' concept; the first cytoplasmic transfer experiment was performed in the mouse during the early 1980s, as a means of overcoming cleavage arrest at the 2-cell stage, the '2-cell block'. Since the first human pregnancy following the transfer of cytoplasm from donor oocytes into the oocytes of a patient with a history of poor embryo development and recurrent implantation failure in 1997, >30 children have been born after direct injection of ooplasm from fresh, mature or immature, or cryopreserved-thawed donor oocytes into recipient oocytes via a modified ICSI technique. Transfer of ooplasm was thus applied with astonishing speed in humans, in the absence of extensive research to evaluate the efficacy and the possible risks of the method. This review focuses on biochemical mechanisms by which transfer of ooplasm might confer a benefit: by correcting a putative imbalance between anti- and pro-apoptotic factors and/or correction of defective mitochondrial membrane potential. We also emphasize the 'empirical' state of this technique, and the related risks.