The geography, tourist attractions and the multiple sites of historical and cultural interest make South America as an important destination chosen by travelers. The continent has a wide climatic variation from north to south, making exposure to risk different between the tropics and the temperate or cold regions. In the countries of tropical South America, the greatest risk is associated with the possibility of acquiring vector-borne diseases, like yellow fever, dengue, malaria and leishmaniasis. The risk of acquiring traveler's diarrhea and food-borne illness is similar across the continent, with some variations according to country and to visit urban or rural areas. Rabies, pertussis and diphtheria have appeared as epidemics in several countries and other diseases such as rickettsiosis, hantavirosis and viral encephalitis have expanded their distribution. The geographic and epidemiological diversity of South America, promotes a challenge for travel medicine specialists because during the pre-travel advice they have to take in account the kind of trip, traveller's medical history, exposure to risk and the dynamics of endemic emerging and reemerging diseases in the region.