OBJECTIVES: Orphan drugs are made to treat, prevent and diagnose orphan or rare diseases. Nevertheless, production of orphan drugs is expensive, while possible earnings are uncertain. Because of this, pharmaceutical companies lose interest in production and commercialization, and when they are offered, they carry high prices, which leads to even further limitations in access and availability. The aim of this study was to evaluate the existing legislations, policies and entities that are responsible for the regulation of orphan drugs in Latin American countries, and their strategies, if any, to improve access for patients. METHODS: Literature search in 7 different databases with free terms, grey literature was also searched. We excluded opinion articles with no factual information. RESULTS: We found documents from ten Latin American countries which had information in topics related with: definition of rare disease, orphan drug legislation, national plans for orphan drugs/rare diseases, orphan drug designation, orphan drug market authorization, market exclusivity, financial and non-financial incentives and pricing. The first country with a recognizable legislation was Panamá in 2001, 18 years after the first legislation, from the US. Additionally, there was no information about incentives, price regulation or control in any of the countries. CONCLUSIONS: There is a lack of specific regulation or at least of publicly available information about orphan drugs regulations in Latin America, which leaves many of the questions unanswered. Argentina and Colombia are the two countries with greater advances in terms of regulation and legislation for orphan drugs, but strategies to improve access are still missing. It is necessary to emphasize the importance of this topic since it will beneficiate people with a diagnosis of an orphan or rare disease, giving them the information they need to be able to access all existing options for diagnosis or treatment.