The potential energy profile for many complex reactions of proteins, such as folding or allosteric conformational change, involves many different scales of molecular motion along the reaction coordinate. Although it is natural to model the dynamics of motion along such rugged energy landscapes as diffusional (the Smoluchowski equation; SE), problems arise because the frictional forces generated by the molecular surround are typically not strong enough to justify the use of the SE. Here, we discuss the fundamental theory behind the SE and note that it may be justified through a master equation when reduced to its continuum limit. However, the SE cannot be used for rough energy landscapes, where the continuum limit is ill defined. Instead, we suggest that one should use a mean first passage time expression derived from a master equation, and show how this approach can be used to glean information about the underlying dynamics of barrier crossing. We note that the potential profile in the SE is that of the microbarriers between conformational substates, and that there is a temperature-dependent, effective friction associated with the long residence time in the microwells that populate the rough landscape. The number of recrossings of the overall barrier is temperature-dependent, governed by the microbarriers and not by the effective friction. We derive an explicit expression for the mean number of recrossings and its temperature dependence. Finally, we note that the mean first passage time can be used as a departure point for measuring the roughness of the landscape.