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The past decade has seen a rapid increase in the number of studies employing psychophysiological methods to explain variation in political attitudes and behavior. However, the collection, analysis, and interpretation of physiological data present novel challenges for political scientists unfamiliar with the underlying biological concepts and technical skills necessary for utilizing this approach. Our objective in this article is to maximize the effectiveness of future work utilizing psychophysiological measurement by providing guidance on how the techniques can be employed most fruitfully as a complement to, not a replacement for, existing methods. We develop clear, step-by-step instructions for how physiological research should be conducted and provide a discussion of the issues commonly faced by scholars working with these measures. Our hope is that this article will be a useful resource for both neophytes and experienced scholars in lowering the start-up costs to doing this work and assessing it as part of the peer review process. More broadly, in the spirit of the open science framework, we aim to foster increased communication, collaboration, and replication of findings across political science labs utilizing psychophysiological methods.