In this paper, the authors discuss why isolate island populations represent a particularly helpful model for genetic epidemiological studies. A thorough previous anthropological research carried out in Eastern Adriatic island isolates, Croatia, in terms of ethnohistory, geography and current demography is reviewed. The major results of the studies of population genetic structure of those populations, including model-bound and model-free approaches, the analyses of serogenetic polymorphisms and most recent studies using HLA class II, VNTR and STR DNA polymorphisms, are briefly presented. The organization of health care on the islands is analyzed and some relevant details of specific medical problems and some autochtonous diseases in these island populations is noted. The authors present in outline four illustrative examples of research opportunities which are afforded by the unique circumstances found in these isolate communities. These relate to hereditary dwarfism on Krk island, Mal de Meleda on Mljet island, extreme inbreeding on Susak island and population genetics of cancer on the islands of Brac, Hvar, Korcula, Vis and Lastovo. Finally, the authors develop objectives and strategies for a long-term genetic epidemiological research of these populations and suggest that such a programme of investigation would further our understanding of the causes of (rare) diseases which are uniquely important to these communities but also of common diseases which are important contributors to the burden of disease both in these islands and throughout the world.