The purpose of this review is to illustrate how tools and concepts from decision and cost-effectiveness analyses can be used to help make decisions in the face of uncertainty and resource constraints, select appropriate subjects for imaging, choose between competing imaging modalities, and prioritize future research. Examples from trauma imaging illustrate the use of the presented tools. The author advocates the PROACTIVE approach in deciding which imaging strategies are cost-effective (PRO for defining the problem, reframing the problem from multiple perspectives, and focusing on the objective; ACT for expanding the alternatives, considering the consequences and associated chances of each alternative, and identifying the trade-offs involved; IVE for integrating the evidence and values, optimizing the value of interest, and exploring uncertainty). Simulation models play an important role in the assessment of imaging strategies by helping to identify alternative strategies and to integrate the best-available evidence related to risks, benefits, patient values, and costs. Exploring the uncertainty in the evidence and assessing the value of obtaining more information can help prioritize future research and guide study design.