Energy exchange is fundamental to life and is a cornerstone in the study of human physiology, metabolism and nutrition. A global effort is underway to further our understanding of human energy exchange and its components as a means of establishing the mechanistic underpinnings of the evolving obesity and chronic disease epidemics. The current report establishes a conceptual historical framework for examining the evolution of energy exchange concepts and measurement methods. We review developments taking place over more than 2000 years during which humans endeavored to establish the source of body heat, the ‘fire of life'. Major conceptual and methodological advances over the past three centuries have incrementally advanced the field and created the energy exchange paradigm within which we now work. As in the past, innovative experimental ideas and measurement methods are now needed to answer important questions brought to light by the obesity and chronic disease epidemics. Nevertheless, older classical measurement methods based on calorimetry techniques still hold a strong position in the field as many diet and weight-related questions remain unanswered.