Background: Spinal cord dysfunction (SCDys) is caused by heterogeneous health conditions, and the incidence is increasing. Despite the growing interest in rehabilitation research for SCDys, research into SCDys faces many challenges. Objective: The objective of this project was to perform a clinical review of changes in SCDys research over the last 4 decades; identify challenges to conducting research in SCDys; and propose opportunities for improving research in SCDys. Methods: A triangulation approach was used for obtaining evidence: literature search (January 2017) using MEDLINE and Embase databases for publications in English (1974-2016) regarding SCDys; workshop discussions at the International Spinal Cord Society annual meeting, September 16, 2016, Vienna, Austria; and our collective expertise in SCDys clinical rehabilitation research. Results: There has been a substantial increase in publications on SCDys over the 4 decades, from 1,825 in 1974-1983 to 11,887 in the decade 2004-2013, along with an improvement in research methodology. Numerous challenges to research in SCDys rehabilitation were grouped into the following themes: (a) identification of cases; (b) study design and data collection; and (c) funding, preclinical, and international research. Opportunities for addressing these were identified. Conclusions: The increase in scientific publications on SCDys highlights the importance of this heterogeneous group among the research community. The overall lack of good quality epidemiological studies regarding incidence, prevalence, and survival in these patients serves as a benchmark for guiding improvements to inform evidence-based care and policy.