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The American quaking aspen (Populus tremuloides Michx.) and its close relative, the Eurasian quaking aspen (Populus tremula L.), cover a realm that is perhaps the most expansive of all tree species in the world. In North America, sudden aspen decline (SAD) is a growing concern that marks the rapid decline of quaking aspen trees leading to mortality at the stand and landscape scale. Research suggests that drought and water stress are the primary causes of SAD. Predisposing factors (age, structure, and landscape position), as well as associated stressors (i.e., pests and pathogens), have been linked to mortality in affected stands. The conflation of multiple interacting factors across the aspen’s broad geographic range in North America has produced significant debate over the classification of SAD as a disease and the proper management of affected stands. Interestingly, no such effects have been reported for the Eurasian aspen. We here review and synthesize the growing body of literature for North America and suggest that SAD is a novel decline disease resulting from multiple inciting and interacting factors related to climate, land-use history, and successional dynamics. We suggest that the range of aspen observed at the onset of the 21st Century was bolstered by a wet period in western North America that coincided with widespread regional cutting and clearing of late-successional forests for timber and grazing. No comparable land-use history, successional status, or age-class structure is apparent or linked for Eurasian forests. Eurasian aspen is either absent or young in managed forests, or old and decadent in parks in Fenno-Scandinavia, or it grows more intimately with a more diverse mixture of tree species that have arisen from a longer period of frequent timber cutting in Russia. Based on these insights we provide recommendations for practical management techniques that can promote stand resilience and recovery across a range of stand conditions in North America. Managers should attempt to identify SAD-prone stands using the presence of predisposing conditions and focus treatments such as coppice or prescribed fire on stands with suitable topographies, elevations, and climates. We conclude that SAD will persist throughout the coming decades, given the enormity of past cutting history, fire exclusion, and current changes in climate until a more active restoration agenda is implemented.