Cell motility is required for many physiological processes (for example, cell movements during development) and is involved in several pathological processes. Benoît Maugis and colleagues have been investigating the motility of the human parasite Entamoeba histolytica and, on page 3884, they propose a new model for bleb-based motility, a poorly studied form of amoeboid locomotion. Blebs are spherical membrane protrusions that are seen in apoptotic, migrating and non-migrating cells, and in cells before they fully adhere to a substrate. The authors show first that E. histolytica, which encounters several environments as it passes through the human body, produces blebs in various microenvironments in vitro. Then, using reflection interference contrast microscopy, they elucidate the relationship between bleb formation and retraction, contact dynamics and net cell motion, and show that bleb-based motility involves the rapid formation of protrusions followed by their stabilisation or retraction. Finally, they use a novel local electroporation method to show that dynamic instability of intracellular pressure drives bleb-based motility. Together, these data establish E. histolytica as a unique model for studying the physical and biological aspects of amoeboid motility.