The accident on November 13, 2002 of the Prestige oil tanker, transporting 77,000 tons of a heavy fuel oil, 50 km off the Galicia coast (NW Spain), and its sinking 200 km offshore after an oil leakage for 6 days started a massive oil spill, affecting more than 800 km of the NW Spanish coast and even some areas of SW France, including the Galicia coast, one of the prime producers of commercial shellfish worldwide. An operational forecasting system, encompassing overflight information, meteorological and oceanographic data collection, and numerical models, was implemented for predicting oil spill trajectories and providing decision makers with technical assessment to respond to the oil spill. This was essential because the massive spreading of the oil made it difficult to respond with the conventional tools. The high density and viscosity of the oil led to the formation of stable emulsions with water, which were broken up into fragments difficult to collect. Converted fishing vessels were advantageously used for open water cleaning operations. The stranding of oil on the coast, which was primarily removed by manual means, was complicated by an unexpected oil burial in sandy beaches reaching to depths up to 4 m. This was directly related to the beach morphodynamics, so a specific forecasting model was developed. Natural attenuation processes were not significant for the removal of oil. Soon after the accident, a large effort was made to monitor the spatial distribution and temporal evolution of hydrocarbons in the different biotic and abiotic compartments, along the northern Spanish coast. This involved the sampling of drifting oil, water, sediments, indigenous populations of mussels, and other biota species. More than 80 sediment stations along the Spanish continental shelf were sampled just after the accident and in 2003–2005. More than 40 coastal stations were also selected for sampling wild bivalves, and an extensive sampling of demersal fish was also performed. Extensive use of the molecular biomarkers in the oil was made in order to confirm the pollution source. In summary, 1 year after the accident, the data showed the high persistence of the spilled heavy oil in the sea with very low incidence of the natural weathering process. The assessment of the accumulation of hydrocarbons in sediments and biota revealed that, with the exception of the coastal areas directly oiled by the spill (Costa da Morte), the polycyclic aromatic hydrocarbons (PAHs) profiles were similar to those generally found in coastal areas influenced by urban/industrial runoff, but even in that area, PAHs in wild mussels declined to background levels about 6 months after the spill. The impact of the oil on biota was studied at the level of biomarker responses as well as different shelf communities and their trophic structure. Populations of benthic species in Costa da Morte (e.g., megrim, lobster, and shrimp) decreased in 2003 but recovered in 2004, whereas no significant effects were detected in demersal communities even though recruits were bound to the same drift of the oil.