To write about dengue retrospective epidemiology is a challenging subject because until laboratory diagnosis tests were developed to confirm human infections by dengue virus (DENV) between 1940 and 1950, all reports about disease or epidemics referred to a generic “dengue/break bone fever/contagious fever/bilious remitting fever.” These nomenclatures employed in past times had perspectives based on medical reports, letters and diaries of people living in the affected areas at the time, and local newspaper reports. As Packard (Bull Hist Med 90(2):193–221) highlighted, the difficulty of using historical sources and “the ambiguous nature” of eighteenth-century disease categories turns the analysis puzzling. Nevertheless, if judiciously used, it can illuminate the history of dengue epidemics over time. In this chapter, we will focus on three periods that were pivotal to shaping our current understanding of dengue disease and epidemiology: (1) First reports of a dengue-like disease and the impact of the infection during the seventeenth and eighteenth centuries; (2) The impact of the II World War (II WW) on the spread of the DENV and its vector worldwide; and (3) The re-introduction of dengue in the Americas and the challenge of Public Health services to control the dramatic escalation of cases and the introduction of new serotypes/genotypes. It is worth mentioning that in the last years, South and Central America and Caribe account for more than 80% of dengue cases in the world (PAHO).