The diagnosis and treatment of human fetal defects has evolved rapidly over the past decade due to improved fetal imaging techniques and better understanding of fetal pathophysiology derived from animal models. The detection of a fetal anomaly may now lead to a change in the timing of delivery, a change in the mode of delivery, or prenatal treatment. Because most therapeutic maneuvers involve some risk to the fetus and mother, there must be a reasonable expectation that the procedure is feasible, safe, and effective before it can be attempted in humans. This requires reliable information about the pathophysiology and natural history of the disease process, the efficacy of fetal surgical intervention in ameliorating the disease, and the feasibility and safety of the proposed intervention. This paper focuses on the rationale and initial clinical experience with fetal surgery for a variety of life-threatening fetal anatomic defects.