The central role of mitochondria in basic physiological processes has rendered this organelle a receiver and integrator of multiple regulatory signals. Steroid and thyroid hormones are major modulators of mitochondrial functions and the question arises as to how these molecules act at the molecular level. The detection in mitochondria of steroid and thyroid hormone receptors suggested their direct action on mitochondrial functions within the context of the organelle. The interaction of the receptors with regulatory elements of the mitochondrial genome and the activation of gene transcription underlies the hormonal stimulation of energy yield. Glucocorticoid activation of hepatocyte RNA synthesis is one of the experimental models exploited in this respect. Furthermore, the interaction of the receptors with apoptotic/antiapoptotic factors is possibly associated with the survival-death effects of the hormones. In addition to the steroid/thyroid hormone receptors, several other receptors belonging to the superfamily of nuclear receptors, as well as transcription factors with well defined nuclear actions, have been found in mitochondria. How these molecules act and interact and how they can affect the broad spectrum of mitochondrial functions is an emerging exciting field.