This thematic issue of the George Wright Forum explores the complexity, multiple benefits, and urgent challenges of landscape-scale conservation, while also identifying a wide range of elements that contribute to success. The issue describes a number of large-scale conservation initiatives. Five case studies are included, ranging from cross-international boundary work in the northern Appalachians and the Rockies to the conservation efforts of the regional watershed of the Potomac; and from the cultural heritage of America’s distinctive regional landscapes to the biodiversity of the Brazilian Atlantic forest.