Only about 30% of successfully fertilized oocytes result in the delivery of a living child. This chapter summarizes current knowledge on the epidemiology, diagnosis, and treatment of first-trimester pregnancy loss. First-trimester pregnancy loss is a common event, experienced by about 25% of all women during their reproductive career. Clinical characteristics of women presenting with first-trimester bleeding are of little value in correctly predicting a miscarriage. The most constant sonographic findings indicative of a miscarriage are those of an empty gestational sac, where no yolk sac and no embryonic pole are present, or the finding of an embryo or fetus without cardiac activity. More recently, progesterone has also been applied in the prevention of miscarriages. At present, three different treatment options are being used in managing first-trimester miscarriages: expectant, surgical and medical management. The available knowledge from randomized controlled trials comparing various treatment options for miscarriages has been systematically reviewed.