In the article on an example of formation and specification of the concepts of mental and physical exhaustion, an analysis of approaches to its study in different periods of early formation of physiology of work has been made. It is shown that interpretation of work as a means of conservation and transformation of the energy of the Sun was first formulated 130 years ago by the national scientist S. A. Podolinsky. The analysis of the heritage of predecessors includes studies conducted by I.M. Sechenov, J.Adamar, K.K.Kekcheev, B.I.Slovtsov, Z. Bakaradze, V.A.Levytskyj, V.V.Rozenblat, M.I. Vinogradov, D.I. Shatenshtein, G.V.Folbort, V.V.Frolkis and other scientists who laid the basis of physiology of work and fatigue teaching. The analysis of the scientific heritage of our predecessors allows us to trace the progress of the development of ideas related to development of the state of fatigue, as well as to emphasize the importance of development of new trends in physiology of work. It is noted that further improvement and search for aspects of physiology of work, not covered by our predecessors, will be useful for modern scholars as certain aspects of it have not been sufficiently analyzed or even overlooked by subsequent generations of researchers.