Parasitic infections are widespread throughout the tropics and sub-tropics, and infection with multiple parasite species is the norm rather than the exception. Despite the ubiquity of polyparasitism, its public health significance has been inadequately studied. Here we review available studies investigating the nutritional and pathological consequences of multiple infections with Plasmodium and helminth infection and, in doing so, encourage a reassessment of the disease burden caused by polyparasitism. The available evidence is conspicuously sparse but is suggestive that multiple human parasite species may have an additive and/or multiplicative impact on nutrition and organ pathology. Existing studies suffer from a number of methodological limitations and adequately designed studies are clearly necessary. Current methods of estimating the potential global morbidity due to parasitic diseases underestimate the health impact of polyparasitism, and possible reasons for this are presented. As international strategies to control multiple parasite species are rolled-out, there is a number of options to investigate the complexity of polyparasitism, and it is hoped that that the parasitological research community will grasp the opportunity to understand better the health of polyparasitism in humans.