After a formal explanation of Mayer's enthalpy balance method as applied to biological reaction rates, the history of its application is traced from Rubner's dog to accounting for the energy of muscle contraction. The introduction of microcalorimetry allowed the method generally to be used for cells in vitro and now particular emphasis can be paid to the growth of cells for the production of therapeutically-important heterologous proteins. In these systems, enthalpy balance studies contribute to defining catabolic processes, designing media, understanding the mechanisms of growth and controlling cultures using heat flux as an on-line sensor of metabolic activity.