Chagas disease, which is caused by Trypanosoma cruzi, is an important health concern owing to the lack of effective drug treatment for chronic infection. A recent study found that although drug treatment rapidly reduced the numbers of T. cruzi in vivo, treatment failed to completely clear the infection. The authors went on to investigate the possible involvement of dormant or non-replicating forms of T. cruzi to explain treatment failure. Indeed, a small fraction of amastigotes (which are the intracellular, non-motile forms of the parasite) was non-replicating during acute and chronic infections in mice. Non-replicating amastigotes differentiated into trypomastigotes, which exited host cells and infected new host cells, where they converted back into replicating amastigotes, with a small number of the progeny again arresting replication. Finally, dormant amastigotes were resistant to extended drug treatment and could re-establish an infection.