Over the past few decades there has not been any significant reduction in the rate of preterm birth. As we enter into a new millennium, prematurity is still the leading cause of perinatal morbidity and mortality in the non-anomalous infant. The only major contributions in reducing perinatal mortality in the preterm infant are those in the field of neonatology, while the area of preterm birth prevention has lagged far behind. This article highlights the research and clinical challenges that stand in the way of making a timely yet accurate diagnosis of preterm labor. In addition, possible pathways in the evolution of preterm labor are discussed with emphasis on their significance to diagnosis and treatment.