South American countries are important agricultural players worldwide. Pesticides are key components of their production systems and, in some cases, complement environmentally sound systems, such as no-till, which contributes to preserving soil productivity. In this review, presented in the symposium Global Perspective on Herbicides Being Banned during the 2019 Weed Science Society of America meeting, we describe the regulatory framework and current situation of restricted and banned herbicides in South America. We also discuss where the pressure for herbicide bans is coming from and the opportunities for improving herbicide use and public perception. Argentina, Brazil, Colombia, and Uruguay were chosen as representative countries of the region. They all have regulatory systems in place for pesticide registration and reevaluation based on science. Glyphosate, paraquat, and some 2,4-D formulations are in the spotlight. Glyphosate is being reevaluated in Brazil and, although banned within the city limits in some cities in Argentina and Uruguay, it can still be used in agriculture. Paraquat is prohibited for aerial applications in Colombia and is the only herbicide that needs a professional prescription in Uruguay. It was reevaluated in Brazil, resulting in a use-restriction phase in effect until 2020, when it will be permanently banned. Ester formulations of 2,4-D have been banned in Brazil since the early 2000s and have restrictions in some provinces in Argentina, where 2,4-D butyl and isobutyl esters will be prohibited starting April 2021. In Uruguay, atrazine is the only herbicide banned for agricultural use. The regulatory frameworks ensure that herbicides on the market are effective and safe. Reevaluation is an important part of the system and is conducted when there are reasonable concerns. There are opportunities to continue training pesticide handlers and applicators and to communicate the importance of adopting the best management practices where herbicides are part of the production system.