The rates of prostate cancer vary by more than 50-fold across different international populations. The aim of this review was to explore the differences in epidemiology and risk factors between the Middle Eastern Arab countries and some of the developed countries in Europe and North America. The age-standardized incidence rate of prostate cancer in the Arab countries is still lower than that in the Western countries, but is steadily increasing with time. Several factors come into play to explain this difference. There are health care systems-related factors such as the lack of good population-based registries, and population-related factors. The latter include the relatively young age structure in the Arab countries, lower reported androgen and prostate-specific antigen levels in Arab men, the effect of genetic differences on prostate cancer risk, the metabolic syndrome paradox, and the protective effect of the Mediterranean diet on a subset of the Arab population. In conclusion, the study of prostate cancer in the Arab world represents a challenge with the currently available cancer care systems and the increase in the burden of the disease. A multinational prospective study to investigate the epidemiology of prostate cancer in the Middle East, with specific attention to country/geographic variability along with a comparative analysis to that of the Western hemisphere is needed.