The Madrean Archipelago or Sky Islands region of the southwestern United States and northern Mexico is recognized for its unique biological diversity, natural beauty, and cultural heritage. This 2012 conference brought together scientists, managers, students, and other interested parties from the United States and Mexico to share their knowledge and passion about the region and to identify needs and creative solutions for existing and emerging problems. More than 300 people attended the conference including a large and energetic contingent from northern Mexico. The conference provided a forum to update the state-of-knowledge that has evolved since the first conference in 1994 and the second conference in 2004. It also provided a setting for the formation of new friendships and partnerships. These proceedings contain 80 of the 190 oral and poster presentations and all abstracts from the plenary sessions and the concurrent sessions. Abstracts in Spanish are included. Topics include climate change in the Sky Island Region, southwestern cienegas, the Northern Jaguar Reserve, amphibian conservation, biodiversity of plants and animals, fire effects, grasslands, and human impacts, and tools. The conference hosted a symposium about Santa Cruz River Watershed Conservation. A lively open forum at the end of the conference generated a list of future scientific and management needs for the Madrean Archipelago and a commitment to increase international cooperation. Mexican participants graciously offered to host the next conference, Speakers stressed the importance for all interested parties to collaborate - to work side-by-side and constantly inform one another about relevant research, timely events, and cross-pollination opportunities throughout the region.