<p>by Andrea L. Graham, David A. Chang van Oordt</p> Why do hosts and parasites vary so much? A new study in PLOS Biology reveals that infection outcomes strongly depend upon interacting effects of host and parasite genotypes, offering an evolutionary explanation for profound and persistent variability. Why do hosts and parasites vary so much? This Primer explores a new study in PLOS Biology revealing that infection outcomes strongly depend upon interacting effects of host and parasite genotypes, offering an evolutionary explanation for profound and persistent variability.