About 12.5% of all maternal deaths in the United States are due to infectious causes. This proportion, although stable during the past three decades, represents an increase in infectious causes of mortality, as the overall mortality rate in U.S. pregnant women had increased steadily during that same period. During healthy pregnancies, a delicate immunological balance-in which a mother’s immune system tolerates the semi-allogeneic fetus yet maintains immune competency against infectious agents-is achieved and maintained. This immunological paradigm, however, results in increased susceptibility to infectious diseases during pregnancy, particularly in later stages and during the early postpartum period. The inflammatory process induced by these infectious insults, as well as some noninfectious insults, occurring during pregnancy can disrupt this carefully achieved balance and, in turn, lead to a state of rampant inflammation, immune activation, and dysregulation with deleterious health outcomes for the mother and fetus. Elucidating mechanisms contributing to the disruption of this immunologic homeostasis, and its disruption by infectious pathogens, might offer opportunities for interventions to reduce maternal and fetal morbidity and mortality.