The Laurentian Great Lakes have experienced recent ecosystem changes that could lead to reductions in adaptive capacity and ultimately a loss of biodiversity and production throughout the food web. Observed changes in Great Lakes benthic communities include declines of native species and widespread success of invasive species like dreissenid mussels in all but Lake Superior. Understanding the ecology of native benthic deepwater preyfish and the reasons for their declines is important for predicting future losses in adaptive capacity and diversity, as well as managing the Great Lakes ecosystem to avoid such losses. Native sculpin species (Cottus bairdii, C. cognatus, C. ricei, Myoxocephalus thompsonii) historically were among the most abundant of the Great Lakes native deepwater benthic preyfish community and are an important link between offshore benthic and pelagic food webs. With one exception, these species have declined in abundance throughout the Great Lakes in recent years, but relatively little is known about their biology and ecology. This review synthesizes the available knowledge for the Great Lakes sculpin species and provides suggestions for future research efforts, which include understanding reproductive ecology and spawning behavior, connectivity and dispersal of populations, early life history, and influences of interactions with native and non-native species.