The ability to contribute consistent, fundamentally sound critiques is an essential element of the scientific peer review process and an important professional skill for investigators. Despite its importance, many students and junior scientists do not have an adequate working knowledge of how to effectively critique research manuscripts. Part of the problem, in our view, is that novice referees often lack a comprehensive understanding of the basic issues that should be considered in evaluating scientific articles. Specifically, they tend to overemphasize certain limitations (usually methodological), while missing other key points related to the scientific method that should be weighed much more heavily. In our journal club and graduate courses we have been using a "checklist" to help graduate students and postdoctoral fellows critically analyze original research papers. In this article we present these guidelines in the hope that they will serve as a helpful resource for students and other novice reviewers when critiquing scientific manuscripts. ADV PHYSIOL EDUC 22: 52-58, 2000.