Freshwater mussels of the order Unionida are currently one of the most imperiled groups of organisms in the North American faunal region. Accurate risk assessments and development of effective management strategies for remaining populations require knowledge of thermal limits in the face of increasing surface water temperature due to climate change and various anthropogenic factors. We conducted a systematic literature review of unionid mussels (order Unionida, families Margaritiferidae and Unionidae) in the North American faunal region to (1) summarize lethal thermal tolerance data by life stage and taxonomy, (2) discuss ecological and climate change implications of existing lethal tolerance data, and (3) identify needs for future research. We identified lethal tolerance estimates for only 28 of 302 species in the families Unionidae and Margaritiferidae. The mean acute median lethal temperatures were 32.8 °C for glochidia (19 species), 35.0 °C for juveniles (13 species), and 36.3 °C for adults (4 species). Generally, glochidia were less tolerant than juveniles or adults of the same species—but there were several exceptions. Generally, Amblemini had the highest acute and chronic thermal tolerance of all tribes followed by Anodontini, Pleurobemini, Lampsilini, and Quadrilini. Acclimation temperature affected lethal tolerance endpoints in less than half (52 of 145) of comparisons within species. Lethal tolerance data for additional species, combined with a comprehensive database of in situ surface water temperatures, would be useful for modeling the frequency and duration of lethal limit exceedance in North America and identifying populations currently living at or near their upper lethal limits.