Increases in energetic demands and/or changes in environmental conditions force organisms to balance changes in ATP demand with an appropriate supply of ATP. Aerobic metabolism has a large capacity for energy production through the flux of oxygen and metabolic substrates (carbohydrates, proteins, and lipids) to working tissue mitochondria. While oxygen pathways are linear from environment to tissue mitochondria, metabolic fuel pathways are complex as fuels can be stored and used in various proportions to ensure adequate ATP supply. This article serves to cover the mechanisms involved with tissue respiration involving the O2 and fuel pathways with an emphasis on fishes.