The red eared slider turtle (Trachemys scripta elegans) is a champion vertebrate facultative anaerobe, capable of surviving for several months under conditions of exceptionally low oxygen availability. The ability of the turtle to facilitate this impressive tolerance to oxygen restriction is accomplished through a dramatic reduction in non-essential cellular processes. This is done in an attempt to conserve limited ATP stores and match demand in the anoxic state, with ATP supplied primarily through anaerobic glycolysis. Determining both the non-essential and the essential cellular processes that are deemed to be anoxia-responsive in the turtle has been an intense area of study over the past few decades. As a result, recent advancements have established the influence of global metabolic controls, such as post-transcriptional and post-translational regulation of gene expression in anoxia adaptation. A remaining question is whether or not epigenetic-level regulatory mechanisms are also utilized to allow for local control over gene expression. Recently, research has begun to document lysine methylation as an anoxia-responsive post-translational histone modification, as the activities of a number of methyl-lysine regulatory enzymes are extraordinarily sensitive to oxygen availability. As a result, oxygen-dependent methyl-lysine regulatory enzymes have been of particular interest to several recent studies of animal oxygen sensitivity, including the freshwater turtle. This review will introduce the concept of lysine methylation as an oxygen-sensitive protein modification as well as a prospectus on how this modification may contribute to anoxia tolerance in the turtle.