Regionally based, collaborative efforts from diverse stakeholders are critical to identify and address diverse and complicated environmental challenges. We present here an example from the Northern Forest Ecoregion of the northeastern United States and southeastern Canada, which currently is being degraded by a variety of simultaneous environmental impacts, including acid rain, fragmentation of landscapes, mercury and salt pollution of water resources, invasive alien species and diseases, and climate change. We propose five sustained, multigenerational actions to protect and restore the vital ecosystem functions of the Northern Forest Ecoregion.