Antarctic subglacial lakes are thought to be extreme habitats for microbial life and may contain important records of ice sheet history and climate change within their lake floor sediments. To find whether or not this is true, and to answer the science questions that would follow, direct measurement and sampling of these environments are required. Ever since the water depth of Vostok Subglacial Lake was shown to be >500 m, attention has been given to how these unique, ancient, and pristine environments may be entered without contamination and adverse disturbance. Several organizations have offered guidelines on the desirable cleanliness and sterility requirements for direct sampling experiments, including the U.S. National Academy of Sciences and the Scientific Committee on Antarctic Research. Here we summarize the scientific protocols and methods being developed for the exploration of Ellsworth Subglacial Lake in West Antarctica, planned for 2012–2013, which we offer as a guide to future subglacial environment research missions. The proposed exploration involves accessing the lake using a hot-water drill and deploying a sampling probe and sediment corer to allow sample collection. We focus here on how this can be undertaken with minimal environmental impact while maximizing scientific return without compromising the environment for future experiments.