A systematic review (SR) is an essential component of evidence-based practice, because it synthesizes information on a particular topic that is necessary to inform health-related decision making. The purpose of this article is to document the process of producing a high-quality SR within the field of rehabilitation in contrast to other fields (eg, pharmaceutic research). We describe the notable methodologic challenges to producing high-quality SRs for rehabilitation researchers. Broadly, we outline how the quality of SRs is evaluated and suggest mechanisms for researchers to address potential pitfalls. Because meaningful SRs can and should be conducted in this field, we provide practical guidance regarding how to conduct such an SR. We outline a series of 8 important steps in the production of an SR: forming a committee, creating a development plan, conducting a literature review, selecting articles for inclusion, extracting data, preparing tables of evidence, facilitating external review and publication, and forming conclusions and recommendations. For each step of the SR process, we provide detailed description about the methodologic decisions involved and recommended strategies that researchers can implement to produce a high-quality SR. Using these preestablished steps and procedures as a guideline will not only help to increase the efficiency of the SR process, but also to improve the quality. The availability of high-quality SRs with plain language summaries promotes access to the best quality information for all involved in decision making.