Hunting by humans played a major role in extirpating terrestrial megafauna on several continents and megafaunal loss continues today in both terrestrial and marine ecosystems. Recent declines of large marine vertebrates that are of little or no commercial value, such as sea turtles, seabirds and marine mammals, have focused attention on the ecological impacts of incidental take, or bycatch, in global fisheries. In spite of the recognition of the problem of bycatch, few comprehensive assessments of its effects have been conducted. Many vulnerable species live in pelagic habitats, making surveys logistically complex and expensive. Bycatch data are sparse and our understanding of the demography of the affected populations is often rudimentary. These factors, combined with the large spatial scales that pelagic vertebrates and fishing fleets cover, make accurate and timely bycatch assessments difficult. Here, we review the current research that addresses these challenging questions in the face of uncertainty, analytical limitations and mounting conservation crises.