During ischemia and heart failure, myocardial cells suffer for chronic energy starvation resulting in metabolic and contractile dysfunction. In normal conditions fatty acids, glucose, and lactate are the principal oxidative fuels in myocardium, while amino acids serve a minor role as an oxidative fuel. However, in pathological conditions, myocardial uptake of several amino acids increases significantly as a consequence of a metabolic remodelling. Amino acids are involved in a variety of key biochemical and physiological activities, that counteract the deleterious cellular effects of reduced oxygen availability. Several amino acids are a direct source of substrate for energy production, and they modulate the activity of some enzymes involved in the glucose metabolism. They increase contractile performance both in isolated animal and human myocardium. Furthermore, amino acids improve the oxidative stress counteracting the action of radical oxygen species, being either precursors of glutathione synthesis, or of substrate of nitric oxide biosynthesis; they act on endothelial function and increase protein synthetic efficiency of myocardial cells by regulating gene expression and modulating hormonal activity. An amount of studies have demonstrated that amino acids administration, on patients with ischemic heart disease and heart failure, can improve several clinical endpoints. Here, we present an overview of the principal effects of the most experienced amino acids and of amino acid derivatives on ischemia and heart failure.