The role of mitochondria in the establishment of developmental competence for the preimplantation mammalian embryo is an area of growing interest for researchers, embryologists and clinicians involved in in vitro fertilization (IVF). This review describes some of the more clinically significant issues in IVF that may be associated with the function and regulation of mitochondria during the earliest stages of embryonic development. In somatic cells, mitochondria have a central role in metabolism, cellular aging and apoptotic cell death, and specific cytopathologies may originate from the accumulation of de novo mitochondrial genetic defects that can effect normal cell and tissue function. Maternally inherited mitochondrial DNA (mtDNA) defects can result in debilitating or lethal conditions for affected individuals (so-called mitochondrial genetic diseases) if genes coding for respiratory chain enzymes are involved (oxidative phosphorylation diseases, OXPHOS). For the oocyte and early embryo, it has been proposed that mutations in the mitochondrial genome may contribute to impaired function and developmental incompetence (Chen et al., 1995; Keefe et al., 1995; Brenner et al., 1998; Barritt et al., 1999,2000). The extent to which specific mtDNA defects are related to early reproductive failure is not clear, but genetic mutations may result in diminished ATP content leading to embryonic abnormalities such as cleavage arrest, slow development, blastomere loss by apoptosis and ultimately, implantation failure (Van Blerkom et al., 1995; Van Blerkom et al., 2000,2001).