Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting the synovium, leading to joint damage and bone destruction and causing severe disability and increased mortality. Several prevalence and incidence studies for RA during the last decades have suggested considerable variations of the disease occurrence among different populations. The majority of the prevalence studies carried out in Northern European and North American countries estimate a prevalence of 0.5 to 1.1%, while the annual incidence varies between about 20 and 50 cases per 100.000 inhabitants. In the last decade studies from Southern Europe and especially from the Mediterranean area showed a different clinical, serological and radiological phenotype for RA as compared to Northern European countries. In subsequent studies it is reported that the majority of RA patients in this area, lack the putative HLA-DRβ motif, which suggest that considerable immunogenetic heterogeneity underlies disease susceptibility in these populations. In addition, studies from Southern European countries report a relatively lower occurrence of the disease. The prevalence rates vary between 0.3 to 0.7%, while the annual incidence is estimated between about 10 to 20 new cases per 100.000 inhabitants. The available data suggest that RA in Southern Europe present a particular genetic, epidemiological and clinical profile. It seems that RA in this area i s less frequent, and milder, with less extraarticular and radiological manifestations. Environmental and life-style factors may contribute to this different profile. Dietary factors such as olive oil and fish consumption and even the Mediterranean diet, could offer a protective effect for disease development and disease severity.