Headwater streams of the Pacific Northwest of North America are home to 52 amphibian species, spanning a diversity of taxa and life histories. Headwater stream-associated amphibians occur both within coldwater-stream channels and throughout adjacent riparian habitat, reflective of the important role of old-growth forests in providing cool, moist microclimates for these sensitive species. Forests of the Pacific Northwest have undergone substantial change over the last century, due to a legacy of resource extraction and ever-evolving forest management practices, as well as climate change. These and other stressors have challenged the adaptive capacity of headwater stream-associated amphibians, as more than half of these species are considered to be of conservation concern at the state, provincial, or federal level in the U.S. and Canada. Here, we overview the primary threats to the persistence of this unique and imperiled taxonomic group and emphasize the urgent need for more research and conservation action to mitigate future decline.