The source of many myths, French Guiana is a unique territory due to the richness of its biodiversity and the diversity of its communities. As the only European territory in the Amazon, surrounded by the vast nation of Brazil and the lesser-known Suriname, Ariane 6 rockets are launched from Kourou, while 50% of the population lives below the poverty line. This paradoxical situation gives rise to health issues specific to this territory, whether they involve infectious diseases caused by unknown pathogens, poisonings, or chronic conditions. Certain infectious diseases such as Q fever, toxoplasmosis, cryptococcosis, or HIV infection are common in temperate countries, but present specific characteristics in French Guiana that sometimes require different medical management and approaches. In addition to these conditions, numerous tropical diseases are also present in an endemic and/or epidemic form, such as malaria, leishmaniasis, Chagas disease, histoplasmosis, or dengue fever. Furthermore, dermatology in the Amazon is extremely diverse, ranging from rare but serious conditions (Buruli ulcer, leprosy) to more common and benign ones such as agouti lice (mites of the Trombiculidae family) or papillonitis. Envenomations by wildlife are not uncommon and require management appropriate to the species involved. Common obstetric, cardiovascular, and metabolic conditions sometimes take on a unique dimension in French Guiana that must be considered in patient care. Finally, practitioners should be familiar with various types of poisoning, particularly heavy metal poisoning. European-level resources offer diagnostic and therapeutic options that do not exist in neighboring countries and regions, thereby enabling the management of diseases that are little known elsewhere. Because of these same European-level resources, research in French Guiana plays a key role within the Amazon region, despite a smaller population than in surrounding countries. Thus, certain conditions such as histoplasmosis in immunocompromised patients, Amazonian toxoplasmosis, or Q fever are virtually undescribed in neighboring countries, likely due to underdiagnosis linked to more limited resources. French Guiana thus plays a leading role in the study of these diseases. The objective of this overview is to guide healthcare providers coming to or practicing in French Guiana in their daily practice, as well as practitioners caring for individuals returning from French Guiana.