Premature rupture of membranes arises from what are likely multifaceted and multistep pathogenic pathways. Pathophysiological processes may involve both endogenous and exogenous fetal and maternal factors. This article reviews and analyzes information regarding, first, the form and function of fetal membranes; second, how membranes physically fail (rupture) at term and preterm gestations; and third, evaluates if we can reduce risks of rupture using physiological understanding and evidence-based clinical studies.