First of all, it’s unclear if it can really live up to its claim to improve overall health by following the diet of our ancestors. While we can all benefit from reducing our intake of processed foods and increasing fruit and vegetable consumption, many dispute whether our ancestors were really all that much healthier than we are today given their significantly shorter life span. In fact, one study even demonstrated that they may have had increased rates of atherosclerosis, or hardened arteries. (5) 
The rationale for the Paleolithic diet derives from proponents' claims relating to evolutionary medicine.[22]:594 Advocates of the diet state that humans were genetically adapted to eating specifically those foods that were readily available to them in their local environments. These foods therefore shaped the nutritional needs of Paleolithic humans. They argue that the physiology and metabolism of modern humans have changed little since the Paleolithic era.[22]:594–95 Natural selection is a long process, and the cultural and lifestyle changes introduced by western culture have occurred quickly. The argument is that modern humans have therefore not been able to adapt to the new circumstances.[23] The agricultural revolution brought the addition of grains and dairy to the diet.[24]

An Interview with Ward Nicholson now has three parts on the web. Good overview of man's diet over the past 65 million years. Long but highly recommended reading. First published in Chet Day's "Health & Beyond" newsletter. Now part of a very comprehensive Beyond Vegetarianism site. Every argument that your vegetarian friends use to avoid meat for health reasons is debunked here.
A number of randomized clinical trials have compared the paleo diet to other eating plans, such as the Mediterranean Diet or the Diabetes Diet. Overall, these trials suggest that a paleo diet may provide some benefits when compared with diets of fruits, vegetables, lean meats, whole grains, legumes and low-fat dairy products. These benefits may include:
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