This is a comprehensive reference book on an essential mitochondrial enzyme, cytochrome c oxidase (COX) – the culmination of four decades of work. This enzyme’s biochemical activity originated and evolved more than a billion years ago. Nevertheless, its contributions to the function of neurons remains relatively obscure. COX is not just a housekeeping enzyme engaged in energy generation, but a treasure trove for the discovery of numerous neuronal properties chronicled in this book. Various methods of studying COX in neurons are described, including biochemistry, histochemistry, cytochemistry, immunohistochemistry, in situ hybridization, and gene isolation. These methods revealed that COX also plays a critical role in rescuing the metabolic integrity of neurons exposed to toxins. The goal of this book is to raise the curiosity of readers to this invaluable enzyme so researchers will continue the quest to uncover neuronal properties unveiled by this enzyme.