Despite the low prevalence of Rare Diseases (RD), over 30 million EU citizens suffer from these conditions. This paper summarizes some aspects of these life-threatening chronic and debilitating diseases that usually require long term specialist care and costly formal and informal surveillance. Epidemiology does have an important role to play in the field of RD, since it provides appropriate methods and tools for assessing exposures and health outcomes. In this regard, the utility of registries, biobanks and population-based surveillance systems are discussed. The lack of effective diagnoses and treatments in RD patients often underlies their shortened life expectancy and quality of life. Due to the limited number of patients and the scarcity of relevant knowledge and expertise, coordination at European level is probably the best way of pooling the very limited resources available and provides a very high added-value. RD require the combined efforts of health and social care professionals, politicians, managers and researchers to increase the availability of effective disease management tools to improve care and to extend both life expectancy and Health Related Quality of Life.