The Principle of Microscopic Reversibility was formulated by Richard Tolman (The Principles of Statistical Mechanics, Dover, New York, 1938) who stated that, at equilibrium, “any molecular process and the reverse of that process will be taking place on the average at the same rate”. Applying this concept to macroscopic systems at local equilibrium leads to the rule of detailed balances (Sect. 2.2) and then, assuming linear relations between thermodynamic forces and fluxes, to the formulation of the celebrated reciprocity relations (Sect. 2.3) derived by Lars Onsager in 1931, and the fluctuation-dissipation theorem, (Sect. 2.4) proved by Herbert Callen and Theodore Welton in 1951. In this chapter, this vast subject matter is treated with a critical attitude, stressing all the hypotheses and their limitations.