The Prairie Pothole Region (PPR) of the United States and Canada is a unique area where shallow depressions created by the scouring action of Pleistocene glaciation interact with mid-continental climate variations to create and maintain a variety of wetland classes. These wetlands possess unique environmental and biotic characteristics that add to the overall regional diversity and production of aquatic invertebrates and the vertebrate wildlife that depend upon them as food. Climatic extremes in the PPR have a profound and dynamic influence on wetland hydrology, hydroperiod, chemistry, and ultimately the biota. Available knowledge of aquatic invertebrates in the PPR suggests that diversity of invertebrates within each wetland class is low. Harsh environmental conditions range from frigid winter temperatures that freeze wetlands and their sediments to hot summer temperatures and drought conditions that create steep salinity gradients and seasonally dry habitats. Consequently, the invertebrate community is composed mostly of ecological generalists that possess the necessary adaptations to tolerate environmental extremes. In this review, we describe the highly dynamic nature of prairie pothole wetlands and suggest that invertebrate studies be evaluated within a conceptual framework that considers important hydrologic, chemical, and climatic events.