Chagas disease is arguably the archetypal neglected disease. Millions of people — the vast majority in Latin America — are infected, yet it is seldom discussed. It has struggled to achieve even a fraction of the notoriety of other neglected diseases, such as malaria. Its prevalence in immigrants to Spain, Portugal, the United States and other parts of the world has gone largely unnoticed. Even those who live in endemic areas are rarely aware of it.

Chagas disease can be mild in the acute stages: the victim might not realize they have been infected. Often the only irritation is the bite mark of the vector, and typical symptoms are indistinguishable from those of other conditions. But, like many parasitic infections, Chagas disease lingers. In around one-third of those infected, the disease resurfaces in a chronic manifestation often decades after the acute stage, with devastating consequences.

There are two main drugs available for acute Chagas disease. These were developed >40 years ago and come with various drawbacks, not least of which being a lack of paediatric formulations — a serious issue given that the majority of acute Chagas disease patients are children. More options are desperately needed.

This Outlook highlights some of the progress in understanding and treating Chagas disease over its 101 years of recent history, covering genomic research, drug development, public-health initiatives and vector-control strategies. It also addresses future concerns — about the potential worldwide threat that Chagas disease poses, and new efforts to control it. Tackling these immense health challenges requires more investment in basic and applied research, and perhaps most importantly, communication of the results to where they can make a difference: let us hope this Nature Outlook marks the beginning of that important conversation.

We are pleased to acknowledge financial support from Eisai, the Drugs for Neglected Diseases Initiative (DNDi), the Pan American Health Organization (PAHO), Fiocruz, Pfizer and Merck & Co., Inc., in producing this Outlook. As always, Nature carries sole responsibility for all editorial content.