Second trimester pregnancy loss is uncommon, but it should be regarded as an important event in a woman's obstetric history. Fetal abnormalities, including chromosomal problems, and maternal anatomic factors, immunologic factors, infection, and thrombophilia should be considered; however, a cause-and-effect relationship may be difficult to establish. A thorough history and physical examination should include inquiries about previous pregnancy loss. Laboratory tests may identify treatable etiologies. Although there is limited evidence that specific interventions improve outcomes, management of contributing maternal factors (e.g., smoking, substance abuse) is essential. Preventive measures, including vaccination and folic acid supplementation, are recommended regardless of risk. Management of associated chromosomal factors requires consultation with a genetic counselor or obstetrician. The family physician can play an important role in helping the patient and her family cope with the emotional aspects of pregnancy loss.