As a result of the dramatic advances made in molecular biology, gene therapy has become viable. The initial endeavors were with monogenetic disorders, but gene therapy may also be of benefit in cancer therapy and treatment of infectious diseases. The current framework for the ethical discussion of gene therapy is a two-dimensional scheme. The first dimension is the target tissue (somatic cells versus germ-line cells) and the second dimension is the purpose (therapy/prevention versus enhancement). Although the mitochondrial genome occurs in eukaryotic cells at several hundred copies and the sequence has been known since the late 1980s, it has been excluded from the ethical discussions of gene therapy or genetic interventions. With the development of the first IVONT protocol and successful experiments with mitochondrial transfection vectors, the two-dimensional framework is no longer adequate. Therefore, we propose a three-dimensional framework for the ethical debate of genetic interventions in humans, whereby we include the genome type (nDNA versus mtDNA) as a third dimension. The ethical evaluation of all imaginable genetic interventions is located on five different levels. The demands for ethical justification are different for each.