Preterm labor (PTL) is defined as uterine irritability accompanied by cervical dilation and/or effecement that occurs before 37 weeks gestation. In most cases, PTL becomes preterm delivery (PTD), accounting for 8% to 10% of births in the United States. Fetuses born before 37 weeks' gestation are at risk for a multitude of health and developmental problems. Most perinatal morbidity and mortality in the United States are caused by PTL. It is a costly problem, in both monetary and human terms. Although some risk factors have been identified, they by no means identify, in advance, every case of PTL and PTD. Despite the understandable emphasis on attempts to find and test risk factors that predict PTL, the ultimate benefit--preventing PTD--will come only from an understanding of the physiologic mechanisms of parturition and how to halt those processes when they occur too early. This article reviews current approaches to preventing PTD, describes the biology of myometrial contraction, and discusses recent progress from several laboratories including the authors' that may shed light on approaches to inhibit uterine contractility in the setting of PTL.