The concept of robustness has the continued potential to shift paradigms in biology by challenging assumed relationships between genotypes and phenotypes. Here we have highlighted some of the empirical evidence for evolution of robustness, and discussed its relevance for evolution of infectious diseases, particularly in humans. Despite the widereaching importance of robustness theory in biology and other disciplines, we emphasize that the origins and implications of robustness may be highly context specific. The underlying causes of diseases in humans and other organisms are manifold. To wield the robustness concept effectively in the evolution of infectious diseases, sufficient understanding of how ecological history might have selected for robustness is warranted. Robustness has often resided in the realm of mathematical theory, but future work would benefit from col-laborations between empiricists and theoreticians to test explicitly predictions using tractable models, or disease pathogens. These efforts would help to elucidate further the role of robustness in past evolution of parasites such as influenza A virus and P. falciparum, and to predict how it might play a role in their future evolutionary change.