This paper reviews some major epidemics in the past 5,000 years in human history and derives 12 lessons in the context of epidemiologic surveillance. The corresponding 12 challenges proposed in this paper could be used to guide us in building a better and more comprehensive surveillance system in the 21st century. This will be achieved by: continuing the evolvement and improvement of surveillance; maintaining on an ongoing basis; being systematic; being population-based; including risk and intervention indicators in the data base; more efficient data analysis; stimulating etiologic research; improving forecasting capability; linking to development of intervention; evaluating the intervention; better ways of information dissemination; and dissemination without prejudice.