During locomotion, muscles use metabolic energy to produce mechanical work (in a more or less efficient way), and energetics and mechanics can be considered as two sides of the same coin, the latter being investigated to understand the former. A mechanical approach based on König's theorem (Fenn's approach) has proved to be a useful tool to elucidate the determinants of the energy cost of locomotion (e.g., the pendulum-like model of walking and the bouncing model of running) and has resulted in many advances in this field. During the past 60 years, this approach has been refined and applied to explore the determinants of energy cost and efficiency in a variety of conditions (e.g., low gravity, unsteady speed). This narrative review aims to summarize current knowledge of the role that mechanical work has played in our understanding of energy cost to date, and to underline how recent developments in analytical methods and their applications in specific locomotion modalities (on a gradient, at low gravity and in unsteady conditions) and in pathological gaits (asymmetric gait pathologies, obese subjects and in the elderly) could continue to push this understanding further. The recent in vivo quantification of new aspects that should be included in the assessment of mechanical work (e.g., frictional internal work and elastic contribution) deserves future research that would improve our knowledge of the