This article discusses mitochondrial pathophysiology, reactive oxygen species, and cardiovascular diseases. Mitochondrial respiratory chains are responsible for energy metabolism/ATP production through the tricyclic antidepressant cycle, coupling of oxidative phosphorylation, and electron transfer. The mitochondrion produces reactive oxygen species as "side products" of respiration. The mitochondrial derived reactive oxygen species is involved in the pathogenesis of various clinical disorders including heart failure, hypoxia, ischemia/reperfusion injury, diabetes, neurodegenerative diseases, and the physiologic process of aging. Observational and mechanistical studies of these pathologic roles of mitochondria are discussed in depth in this article.