On April 20, 2010, the explosion of the Deepwater Horizon (DWH) oil rig resulted in the loss of 11 lives and the largest oil spill in US history (Graham et al., 2010) and perhaps the second largest in the world, after the first Gulf War Oil Spill from Kuwait. Over the 84 days following the explosion, an estimated 6.7 x 105 mT of Louisiana Sweet Crude oil (United States Government, 2011) and up to 500,000 mT of methane and gases (Joye et al., 2011) were released from 1,480 m below the ocean's surface into the Gulf of Mexico (GoM). As oil continued to escape from the seafloor throughout the summer of 2010, images of oiled wildlife pervaded the news. These pictures, though troubling, only hinted at the fate of the plankton that form the foundation of the GoM ecosystem. This review discusses the potential effects of the DWH oil spill on the overlooked, but extremely important, members of the GoM ecosystem—the plankton. Our assessment is based on data collected in the aftermath of the DWH spill and supplemented with studies from past oil spills when information on the GoM spill was limited or unavailable. The time line we develop traces the spill from a "planktonic perspective," emphasizing the population dynamics of marine bacteria, phytoplankton, zooplankton, and fish larvae.