The physiologic changes of pregnancy and the puerperium and their effect on antibiotic therapy have not received widespread attention. Pregnancy is accompanied by multiple physiologic changes, including increased uterine weight, blood volume, extracellular fluid, endometrial blood flow and renal function changes. Those changes affect therapy for endometritis since it may take several weeks for a return to the pregravid state. Preeclampsia is associated with reductions in intravascular space, increased extravascular space from edema and impaired renal function. Postpartum uterine changes may also complicate drug therapy because of poor antibiotic perfusion. The ideal antibiotic for postpartum endometritis would achieve optimal uterine tissue levels, be administered infrequently, and have adequate activity against anaerobes and minimal toxicity.