Evidence for severe declines in large predatory fishes is increasing around the world. Because of its long history of intense fishing, the Mediterranean Sea offers a unique perspective on fish population declines over historical timescales. We used a diverse set of records dating back to the early 19th and mid 20th century to reconstruct long-term population trends of large predatory sharks in the northwestern Mediterranean Sea. We compiled 9 time series of abundance indices from commercial and recreational fishery landings, scientific surveys, and sighting records. Generalized linear models were used to extract instantaneous rates of change from each data set, and a meta-analysis was conducted to compare population trends. Only 5 of the 20 species we considered had sufficient records for analysis. Hammerhead (Sphyrna spp.), blue (Prionace glauca), mackerel (Isurus oxyrinchus and Lamna nasus), and thresher sharks (Alopias vulpinus) declined between 96 and 99.99% relative to their former abundance. According to World Conservation Union (IUCN) criteria, these species would be considered critically endangered. So far, the lack of quantitative population assessments has impeded shark conservation in the Mediterranean Sea. Our study fills this critical information gap, suggesting that current levels of exploitation put large sharks at risk of extinction in the Mediterranean Sea. Possible ecosystem effects of these losses involve a disruption of top-down control and a release of midlevel consumers.