A commonly stated assumption about our genetic heritage is that we humans are basically quasi-identical to the hunter-gatherers of the Old Stone Age, and our differentiation from those is due to the acquisition of culture at an increasing rate since the beginning of the Neolithic.
This assumption is used to explain many of the ills of modern man, and to propose solutions, such as the Paleolithic diet. According to its adherents, human beings must adjust their environment and lifestyle to mimic aspects of the Paleolithic.
The main argument in favor of this idea is that the Paleolithic has lasted a lot longer than more recent geological ages. In other words, there has not been enough time to shake up our hunter-gatherer genes.
In some cases, e.g., those of as hunter-gatherer tribes who have recently made the transition to agriculture and settled life, there can be no doubt that this assumption is correct. However, the majority of human beings are descended from ancestors who adopted food producing subsistence methods thousands of years ago; a short time in geological terms, but measuring in hundreds of generations.
The rate of evolutionary change is not a constant. It is a function of the rate of mutation, which creates new genetic variants (1) and of selection intensity which shifts allele frequencies around. The latter is a function of the rate at which the environment changes, and this depends on both the rate of cultural and ecological change (2), but also on the rate of migration, since migration brings people into new environments for which they are not yet adapted.
Clearly, the rate of cultural change has been significant since the Paleolithic, and so must have been the rate of migration, judging and extrapolating from the historical period. Hence, it is not unlikely that we may have evolved quite a bit since our hunter-gatherer ancestors, and indeed, changes in body and head form, documented for recent as well as older human groups should find parallels in the evolution of other human attributes, both behavioral and physical.
A case in point is the issue of racial differences, where it is often claimed that human races differ from each other due to their exposure to "hard winters" or "tropical climates" during the Paleolithic age. This can of course be substantiated for some primary racial characters which survive in the record, but as Vincent Sarich points out, human racial variation may be of much more recent origin, and is certainly not as marked in older periods. And, of course, in many cases it may not be genetic in origin, especially in behavior qualities which are much more malleable than physical ones.
A case can be made that human beings are maladapted for modern living conditions, and that this results in selection, e.g., on the road, or in the bedroom. But, this should lead us into thinking that perhaps the modern lifestyle -as opposed to the premodern, not the Paleolithic one- is to blame.
This idea is also supported by a review of the paleoanthropological record which does indeed show an increase in disease, decrease in stature, etc. after the Neolithic transition, but also shows a marked in this and other attributes after the initial cultural shock, which continued -with fluctuations- until present times, with modern humans in developed nations being taller than all preceding ones (3).
It is not now that our Paleolithic genomes find themselves in a strange new world for which they are poorly designed; that crisis had already occurred thousands of years in the past. We would be better off thinking about the easing the ills of our present transformation into industrial and post-industrial beings, instead of idealizing the Paleolithic past, or joining chimerical battles against civilization.
(1) And which can be expected to be a constant in most cases, but see this post on the evolution of evolvability for exceptions to this rule.
(2) Until the modern age, man was probably not able to effect planetary scale ecological change, but he did create significant local changes, by e.g., clearing forests or building edifices; it is the immediate environment, which is most man-made and which most affects man.
(3) I have dealt with the arguments of those bemoaning the rise of degenerative disease rates elsewhere.