Mitochondria are sources of energy production through their role in producing adenosine triphosphate for cell metabolism. Defective mitochondrial biogenesis and function play relevant roles in the pathophysiology of relevant diseases, including obesity, diabetes mellitus, myopathies, and neurodegenerative diseases. Their function is the product of synthesis of macromolecules within the mitochondria and import of proteins and lipids synthesized outside the organelles. Both are required for mitochondrial proliferation and may also facilitate the growth of preexisting mitochondria. Recent evidence indicates that these events are regulated in a complex way by several agonists and environmental conditions, through activation of specific signaling pathways and transcription factors. Nitric oxide (NO) appears to be a novel modulator of mitochondrial biogenesis. High levels of NO acutely inhibit cell respiration by binding to cytochrome c oxidase. Conversely, chronic, low-grade increases of NO stimulate mitochondrial biogenesis in diverse cell types. Here, we suggest that some types of nutrients, including specific mixtures of amino acids, may improve mitochondrial biogenesis and energy production in energy-defective conditions by increasing endothelial NO synthase expression.