Molecular machines use external energy to drive transport, to do mechanical, osmotic, or electrical work on the environment, and to form structure. In this paper the fundamental difference between the design principles necessary for a molecular machine to use light or external modulation of thermodynamic parameters as an energy sourcevs.the design principle for using an exergonic chemical reaction as a fuel will be explored. The key difference is that for catalytically-driven motors microscopic reversibility must hold arbitrarily far from equilibrium. Applying the constraints of microscopic reversibility assures that a coarse grained model is consistent with an underlying model for motion on a single time-independent potential energy surface. In contrast, light-driven processes, and processes driven by external modulation of the thermodynamic parameters of a system cannot in general be described in terms of motion on a single time-independent potential energy surface, and the rate constants are not constrained by microscopic reversibility. The results presented here call into question the value of the so-called power stroke model as an explanation of the function of autonomous chemically-driven molecular machines such as are commonly found in biology.