Toxoplasma gondii is a protozoan parasite that is globally widespread and causes a common infection of many warm-blooded animals. It has an unusual population structure with a few clonally reproducing strains apparently dominating in many of its hosts, which include humans. In mice, the various strains of the parasite differ enormously in their virulence and disease presentation. In humans, disease manifestations are highly variable, ranging from asymptomatic to severe, especially in cases of brain and eye infection. Recent data suggest that, as with mice, at least part of this variability in human infection may be tied to the type of strain that causes the infection. Improvements in our knowledge of this parasite's population biology and ways to determine the genotype of an infecting strain should make it possible to test this relationship in various disease scenarios. Clear correlations will substantially affect the management of human disease, matching an aggressive infection with an equally aggressive treatment.