The Apache Highlands ecoregion incorporates the entire Madrean Archipelago/Sky Island region. We analyzed the current distribution of 223 target species and 26 terrestrial ecological systems there, and compared them with constraints on ecosystem integrity (e.g., road density) to determine the most efficient set of areas needed to maintain current biodiversity. The resulting portfolio of 90 areas includes 12.5 million acres (5 million ha) that should be priorities for protection. Conservation strategies include protection and restoration of grasslands, restoration or maintenance of natural fire regimes, and learning more of probable effects of climate change.