The Gulf of Mexico is an oceanic basin characterized by extensive hydrocarbon reserves. The western and central portions of the Gulf’s continental slope are subject to natural seepage of oil and gas into overlying sediments and waters. Natural seeps provide valuable laboratories for studying how chemical and biological processes respond to hydrocarbon inputs such as might happen from anthropogenic activity such as the Deepwater Horizon accident in 2010. These seeps provide modest inputs (<3% of the daily discharge of the Deepwater Horizon accident) of oil and gas over hundreds to thousands of years of ecological integration. ECOGIG-2 (Ecosystem Impacts of Oil and Gas Inputs to the Gulf – 2) is a multiscale, multidisciplinary study of the impacts and fates of oil and gas released in offshore waters of the Gulf of Mexico. The central concept framing ECOGIG-2 is that the Gulf’s ecosystem is preconditioned by natural seeps to mitigate what would otherwise be even more substantial and widespread damage from disruptive hydrocarbon discharges due to natural events and anthropogenic activity. Microbial oceanographers Andy Juhl and Ajit Subramaniam are working with organic geochemist Beizhan Yan and physical oceanographer Andreas Thurnherr to understand the composition of the hydrocarbons, their transport, and impact on the microbial ecosystem of the Gulf of Mexico.