The civilizations in the Mediterranean Sea have deeply changed the local environment, especially with the extraction of subsurface oil and gas, their refinery and transportation. Major environmental impacts are affecting all the sides of the basin with actual and potential natural and socio-economic problems. Events like the recent BP's oil disaster in the Gulf of Mexico would have a tremendous impact on a close basin like the Mediterranean Sea. The recently EU-funded project ULIXES (http://www.ulixes.unimi.it) aims to unravel, categorize, catalogue, exploit and manage the microbial diversity available in the Mediterranean Sea for addressing bioremediation of polluted marine sites. The rationale of the project is based on the multiple diverse environmental niches of the Mediterranean Sea and the huge range of microorganisms inhabiting therein. Microbial consortia and their ecology, their components or products are used for designing novel pollutant- and site-tailored bioremediation approaches. ULIXES exploits microbial resource mining by the isolation of novel microorganisms as well as by novel advanced 'meta-omics' technologies for solving pollution of three major high priority pollutant classes, petroleum hydrocarbons, chlorinated compounds and heavy metals. A network of twelve European and Southern Mediterranean partners is exploring the microbial diversity and ecology associated to a large set of polluted environmental matrices including seashore sands, lagoons, harbors and deep-sea sediments, oil tanker shipwreck sites, as well as coastal and deep sea natural sites where hydrocarbon seepages occur. The mined collections are exploited for developing novel bioremediation processes to be tested in ex situ and in situ field bioremediation trials.