New findings What is the topic of this review? This narrative review explores past and recent findings on the mechanical determinants of energy cost during human locomotion, obtained by using a mechanical approach based on Konig's theorem (Fenn's approach). What advances does it highlight? Recent developments in analytical methods and of their applications allow a better understanding of the mechanical-bioenergetic interaction. Advances are: 1) the determination of "frictional" internal work; 2) the association between tendon work and apparent efficiency; 3) a better understanding of the role of energy recovery and internal work in pathological gait (amputees, stroke and obese); 4) a comprehensive analysis of human locomotion in (simulated) low gravity conditions. Abstract During locomotion, muscles use metabolic energy to produce mechanical work (in a more or less efficient way); as a matter of fact, 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 Konig'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 last 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, un-steady speed). This narrative review aims to summarise current knowledge about 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 un-steady 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) deserve future research and would improve our knowledge on the mechanical-bioenergetic interaction during human locomotion, as well as in sport science and space exploration. This article is protected by copyright. All rights reserved.