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Naturally occurring mixtures of hardwoods and softwoods are found throughout the eastern United States and Canada. They are compositionally diverse and appear to have originated from a complex array of natural disturbances or past harvesting. Contemporary mixedwood stands can be difficult to regenerate and manage because individual species of these mixtures have differing shade tolerances, growth rates, longevities, phenology, and crown and root structure. Consequently, they often cannot be sustained without deliberate silvicultural efforts to regenerate and recruit desirable species. Despite the difficulties, foresters are interested in managing hardwood-softwood mixtures because of the many benefits that they confer including increased resistance to pests and diseases, improved habitat diversity, enhanced climate change resilience and adaptability, and increased diversity of forest products. The interest in and the challenges related to managing these mixtures have led to the development of many research-management partnerships across the eastern United States and Canada to resolve regeneration and recruitment problems. Here we discuss the regeneration and recruitment challenges for a variety of hardwood-softwood mixtures across the eastern United States, identify the research-management partnerships that have developed to address them, and describe how these partnerships are leading to solutions.