Although clinical guidelines may have substantial implications for allocation of health-care resources, these issues typically are not considered in the guideline development process or are only considered informally. This is a particular challenge for guidelines intended to be applicable in a diversity of settings. Based on theoretical and practical issues, we develop and apply a basic strategy for incorporating resource considerations into clinical guidelines. Formal economic assessments, such as cost-effectiveness analyses, provide a powerful tool to account for the health and economic implications of clinical guidelines. An acceptable tradeoff of money for health can depend highly on local considerations, and it is feasible to incorporate resource considerations into clinical guidelines. Although use of a “bright line” criterion for what constitutes an acceptable tradeoff of money for health has some appeal, this approach can lead to guidelines that are sensible in some contexts but unrealistic in others. One way to address this tension is through “resource aware” guidelines in which the recommendations are primarily based on scientific evaluations of efficacy supplemented by a review of evidence about the health and economic tradeoffs associated with various options. This approach limits the possibility that the guideline committee can make a universal recommendation based on resource considerations, but we expect it will encourage more thoughtful discussion of economic issues; greater sensitivity to the diversity of investment in health resource internationally; and, perhaps, innovative ways of overcoming resource barriers to the use of the most effective therapies.