Like many infectious agents, malaria parasite populations harbor antigenic diversity because it confers a fitness advantage in the context of adaptive host immunity. Antigenic diversity is not unstructured, however. It is organized by rules deriving from humoral and/or cellular cross-protective immunity, and it is bounded by functional constraint. If better understood, these rules that structure antigenic diversity could inform the rational design of future vaccines. Though the first malaria vaccine was licensed in 2015 following three decades of development, work continues to develop a malaria vaccination program with improved duration and magnitude of protection. A long-term goal of our group is to discern rules that structure the genetic diversity in malaria parasite antigens, with the ultimate objective of supporting the development of more highly efficacious multivalent vaccines.