The aim of this chapter is to focus on the causative factors. This chapter is divided into seven parts, which include etiopathogenesis of preterm labor, infection in preterm labor, anatomical factors in preterm labor, medical and systemic disorders in preterm labor, multiple pregnancies and preterm labor, assisted reproductive technique and preterm labor, and iatrogenic causes of preterm labor. The pathophysiology of preterm birth is multifactorial, very complex, and not clearly understood. Several genetic, physiological, and environmental factors are associated with preterm birth and contribute to uterine activation, labor, and birth. In the recent years increasing assisted reproduction techniques, increasing rates of multiple births and the resultant increasing obstetric intervention have also lead to the increase in preterm labor. Preterm labor has multifactorial etiology, of which the anatomical causes account for 9%. A preterm birth could be spontaneous or indicated means the one that is induced. There are number of maternal medical conditions that are associated with either spontaneous or induced preterm labor.