The hemoflagellate protozoan parasite Trypanosoma cruzi is the causative agent of the Chagas disease, a progressive fatal cardiomyopathy that afflicts more than 20 million people in Central and South America. The T. cruzi life cycle is affected by changes in temperature and pH, the parasite replication being facilitated in mammalian hosts rather than in insect vectors. Here, we postulate that the modulation of key enzymes by pH- and temperature-dependent substrate inhibition may affect the T. cruzi life cycle and limit the geographic range covered by the parasite.