Diseases resulting from mutations in mitochondrial DNA (mtDNA) are inherited by all offspring through the maternal lineage. Multiple organs are severely affected, no preventative treatments are available and most patients experience a poor quality of life or early death. With developments in mitochondrial transfer techniques, hope for preventing transmission of mutated mtDNA onto offspring is emerging. Many ethical issues have been raised regarding such treatments, which involve transfer of nuclear material into donated oocytes with healthy mitochondria, or the introduction of healthy donor mitochondria into affected oocytes. Blastomere, ooplasmic, pronuclear and spindle transfer have been explored. Ethical concerns relate to (a) the alteration of germ line genetics and (b) the dilemma of children inheriting DNA material from three instead of two parents. In contrast to gene therapy, where only the DNA of the treated individual is altered, these techniques involve the introduction of foreign mtDNA into the germ line that will be inherited by all children in downstream generations. Mitochondrial transfer has also been closely associated with reproductive cloning, which is regulated differently worldwide. Children born from these techniques might experience an identity crisis. Although three gametes are needed to produce a healthy embryo in this scenario, the child will inherit all nuclear DNA from the intending parents, while only inheriting mtDNA from the donor. Social and scientific values must be considered when introducing new healthcare technology. Many believe that some assisted reproductive technology techniques go beyond the limits of acceptable medical intervention. But who ultimately decides what is acceptable? We address the ethical and social issues surrounding this emerging new technology, legal developments regarding its clinical introduction in the UK and the USA, the future impact on technique and patient management, and relevant legislation in South Africa.