The relationship between seafood eaten during pregnancy and neurocognition in offspring has been the subject of considerable scientific study for over 25 years. Evaluation of this question led two scientific advisory committees to the Dietary Guidelines for Americans (DGAC), the Food and Agriculture Organization of the United Nations with the World Health Organization (FAO/WHO), Health Canada, the European Food Safety Authority (EFSA), and the U.S. Food and Drug Administration (FDA) to conclude through 2014 that seafood consumed by pregnant women is likely to benefit the neurocognitive development of their children. The evidence they reviewed included between four and ten studies of seafood consumption during pregnancy that reported beneficial associations. In contrast there are now 29 seafood consumption studies available describing over 100,000 mothers-child pairs and 15 studies describing over 25,000 children who ate seafood. A systematic review of these studies using Nutrition Evaluation Systematic Review methodology is warranted to determine whether recent research corroborates, builds on, or significantly alters the previous conclusions. Studies that evaluate the integrated effects of seafood as a complete food more directly and completely evaluate impacts on neurocognition as compared to studies that evaluate individual nutritients or toxicological constituents in isolation. Here we address how the findings could add to our understanding of whether seafood consumed during pregnancy and early childhood affects neurocognition, including whether such effects are clinically meaningful, lasting, related to amounts consumed, and affected by any neurotoxicants that may be present, particularly mercury, which is present at varying levels in essentially all seafood. We provide the history, context and rationale for reexamining these questions in light of currently available data.