This review outlines the limitations of current techniques for evaluating the Mediterranean diet in Mediterranean versus non-Mediterranean populations. Differences between the two populations with regard to the foods that are available, food processing and preparation techniques, and eating and lifestyle habits may influence the implementation and effects of a Mediterranean diet in non-Mediterranean regions. For example, the composition of food groups may vary significantly, due to differences in the specific foods within a food group and to differences in aspects of food production and preparation. Notable differences between the diets of Mediterranean versus non-Mediterranean populations include the source of monounsaturated fatty acids (olive oil versus meat), the amount of vegetables consumed and their manner of preparation, the source of alcohol (wine versus other) and the pattern of intake, and the types of meat and dairy products consumed. Lifestyle factors such as meal patterns and exposure to sunlight may also act as confounding factors when the overall benefits of a Mediterranean diet are assessed. Improving the calculation of Mediterranean diet scores and measuring plasma nutrient levels may help mitigate the effects of confounders. These considerations could have important health implications when a Mediterranean diet is implemented by non-Mediterranean populations.