This book contains five chapters exploring the structure and function of cytochromes, which are redox-active proteins that contain a heme with a central Fe atom at its core as a cofactor. Chapter One explores the functional relevance of cytochrome c-oxidase subunit IV isoform expression for cellular energy sensing, ATP production, and oxidative stress levels and its role in neurodegeneration. Chapter Two deals with the factors determining the orientation of ligated histadines in hemoproteins, cytochromes, and model systems. Chapters Three and Four include comparative studies of native and synthetic cytochrome b. Lastly, Chapter Five discusses some examples of synthetic and native cytochromes used as central components of biosensors in bioelectronic/biocatalytic applications.