In recent decades incidence of non-insulin-dependent diabetes mellitus has increased to epidemic proportions in several traditional populations due to changes in their lifestyles from those of hunters, gatherers and subsistence agriculturists to a contemporary pattern whose central features are sedentary occupations and high-energy fuel resources. As a result, non-infectious perturbations such as non-insulin-dependent diabetes mellitus, hypertension and cardiovascular diseases emerge as the major causes of morbidity and mortality both in developing and in developed nations. Currently, the highest non-insulin-dependent diabetes mellitus prevalences are found in populations that have undergone rapid alterations in lifestyle, such as Australian Aborigines, native Americans, Pacific islanders and some migrant populations like the Asian Indians. This review focuses on non-insulin-dependent diabetes mellitus as a prime instance of the 'thrifty genotype' and its interrelationship with glucose intolerance as a prime risk factor for cardiovascular diseases including hypertension, dyslipidaemia and hyperinsulinaemia. An alternative hypothesis, namely the 'thrifty phenotype' hypothesis, challenging the genotype hypothesis is hereby presented. The review is presented to provide insight for clinical application of these hypotheses in future studies concerning the prevention and intervention strategy of non-communicable disorders. A comprehensive application of these strategies would be beneficial to researchers, clinicians and patients.