A key outcome of evolution by natural selection is adaptation. Since the beginning of the age of genetics, evolutionary biologists have focused on the evolution of nuclear genes as the basis for adaptation. Changes to the mitochondrial genome were long viewed as the result of drift and unimportant to organism fitness. New theory and empirical observations, however, are implicating changes in mitochondrial function as a central component of adaptation related to temperature, oxygen pressure, and diet. Novel mitochondrial function underlying adaptive evolution is a product of interacting mitochondrial and nuclear genes to create changes to the electron transport system, and variation in mitochondrial genotypes has been found to play a key role in such adaptive evolution of eukaryotes. Evidence is emerging that changes in mitochondrial function resulting from mitonuclear coevolution underlie key evolutionary innovations associated with major adaptive radiations including the transition from terrestrial locomotion to flight. I discuss the empirical evidence that supports a key role for mitonuclear coevolution in adaptation and adaptive radiation and the implications for fundamental ideas in ecology and evolution.