The respiration of dissolved organic matter by heterotrophic bacteria and Archaea represents the largest sink in the global marine biological carbon cycle, an important constraint on organic carbon supply, and the major driver of global elemental nutrient cycles. Direct measurement of heterotrophic production and respiration is difficult. However, the recent development of methods involving in vivo electron transport system activity, bioassay uptake of specific prokaryotic substrates, and nutrient addition incubations are poised to discern the complex interactions between metabolic rate, community structure, and organic and inorganic nutrient availability. In a changing global environment, it is important to understand how increasing sea surface temperature, melting sea ice, ocean acidification, variable dust deposition, and upwelling intensity will impact the metabolism of Bacteria and Archaea and so the balance between carbon sequestration and carbon dioxide evasion to the atmosphere. Continued and improved measures of prokaryotic production and respiration are vital components of this endeavor.