Chagas disease is a debilitating human illness caused by infection with the protozoan Trypanosoma cruzi. A capacity to invade and replicate within many different cell types is a cornerstone of the remarkable fitness of this parasite. Although invasion occurs independently of actin polymerization, the host cell still participates in the process, often in unexpected ways. Recent surprising findings indicate that host-cell lysosomes are indispensable, either by directly mediating invasion or by retaining these highly motile parasites inside cells.