Questions concerning the long-term effects of early experience on psychological development in humans continue to stir up controversy. There are, at present, great diversity and contradictions among extant conceptual models and inadequate data to resolve these differences. Limited opportunities to use experimental approaches and the inherent restrictions of observational approaches in research on humans implies that alternative research designs are needed. This article examines the use of “natural experiments” as a method for testing hypotheses concerning the effects of early experience on psychological development. The benefits and limitations of using natural experiments are reviewed and several case illustrations are considered.