Reef managers cannot fight global warming through mitigation at local scale, but they can use information on thermal patterns to plan for reserve networks that maximize the probability of persistence of their reef system. Here we assess previous methods for the design of reserves for climate change and present a new approach to prioritize areas for conservation that leverages the most desirable properties of previous approaches. The new method moves the science of reserve design for climate change a step forwards by: (1) recognizing the role of seasonal acclimation in increasing the limits of environmental tolerance of corals and ameliorating the bleaching response; (2) using the best proxy for acclimatization currently available; (3) including information from several bleaching events, which frequency is likely to increase in the future; (4) assessing relevant variability at country scales, where most management plans are carried out. We demonstrate the method in Honduras, where a reassessment of the marine spatial plan is in progress. Copyright: ß 2014 Chollett et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: The authors confirm that all data underlying the findings are fully available without restriction. The permanent link to access the data on PANGEA is (?http://dx.doi.org/10.1594/PANGAEA.836153). Funding: The research leading to these results has received funding from the European Union 7th Framework programme (P7/2007–2013) under grant agreement no. 244161, Pew (grant 2008-000330-010) and ARC Laureate Fellowships (FL0992179) to PJM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist.