The reintroduction of the Eastern Migratory Population of Whooping Cranes (Grus americana) has shown the most promise of any effort to date toward the establishment of a self-sustaining population. However, reproduction – including both nest success and chick survival – has been a major challenge. Here, we review the research and management efforts deployed to identify and address this challenge. While there is evidence that a proximal cause of nest failure is harassment by blood-feeding black flies (Simulium spp.), this is not likely to be the only contributing factor, and we present alternative hypotheses. There is less understanding of the causes of poor chick survival, and we present hypotheses for factors that may be contributing to chick mortality, including environmental, genetic, and behavioral factors. For both nest success and chick survival, we carried out a value of information analysis, using expert judgment, which allowed us to prioritize the alternative hypotheses for evaluation based on the expected management benefit of addressing each hypothesis. On the horizon are multiple opportunities to explore hypotheses about environmental factors as well as genetic and behavioral characteristics of the birds themselves that may contribute to poor reproduction. If bird-specific characteristics, such as genetics or rearing methods, are hindering reproduction, this has important implications for all efforts to restore Whooping Crane populations.