In August 2016, scientists from the United States and Mexico assembled at Highlands, North Carolina, a temperate-zone hot spot of salamander biodiversity, to participate in the Special Highlands Conference on Plethodontid Salamander Biology. Hosted by the Highlands Biological Station (HBS), the conference celebrated the 90th year of the HBS, and especially the productive collaboration at Highlands of Drs. Lynne Houck, Steve Arnold, and Rick and Pam Feldhoff. The conference showcased the increasing value of plethodontids as research models, exemplified by eight papers in this special issue of Herpetologica stemming from invited minireviews presented at the 2016 Special Conference. The papers contribute to the dramatic rise in journal articles that use plethodontids to address diverse questions of broad relevance to modern biology. We hope that this special issue of Herpetologica sparks new research on these fascinating salamanders, and we look forward to future conferences on plethodontid salamander biology.