Pregnancy-related death is defined by the International Classification of Diseases, Tenth Revision (ICD-10) as the death of a woman while pregnant or within 42 days of termination of pregnancy, irrespective of the cause of death. In the year 2000, a collaborative effort involving World Health Organization (WHO), UNICEF, and UNFPA estimated 660 maternal deaths in the United States. This averages 11 maternal deaths per 100,000 live births reported. Many pregnancy-associated deaths are not easily identified as such since the presence of a recent or current pregnancy may not be listed on the death certificate. Thus, the WHO estimates that in the United States, the maternal mortality is approximately 17/100,000 pregnancies. This is significantly higher than the goal set by the US Department of Health and Human Services in Healthy People 2010, which sets the target for maternal mortality at less than 3.3/100,000 live births. The most common causes of maternal death vary somewhat from region to region in the United States. They include pulmonary thromboembolism, amniotic fluid embolism, primary postpartum uterine hemorrhage, infection, and complications of hypertension including preeclampsia and eclampsia. Pulmonary disease, complications of anesthesia, and cardiomyopathy also are significant contributors to maternal mortality in some populations. The death of a pregnant or recently pregnant individual poses a wide scope of challenges to the forensic pathologist and investigator. The pathologist must have a broad knowledge of the physiologic and biochemical changes that occur during pregnancy, as well as the clinical and pathological manifestation of these changes. Conditions that may be "benign" in the nonpregnant individual may be lethal in the puerperal period. In addition, it should be kept in mind that deaths during pregnancy may be due to unnatural causes. Accident, homicide, and suicide must be ruled out in each case. The authors reviewed all forensic cases referred for autopsy to the Forensic Section of the Medical University of South Carolina from January 1989 through December 2003. All decedents listed as pregnant or postpartum were analyzed as to maternal age, race, past medical history, previous pregnancies and outcome, prenatal care, gestational age, fetal or neonatal outcome, location of delivery, placental findings, maternal autopsy findings, toxicology, cause of death, manner of death, and fetal or neonatal autopsy findings. The authors present this retrospective study to better determine the factors leading to maternal demise and discuss the autopsy/ancillary techniques useful in determining the cause of death in this challenging area.