Rheumatoid arthritis (RA) is the most prevalent cause of chronic arthritis worldwide and contributes substantial health burden and socioeconomic costs, issues that are magnified by the aging population. Despite significantly improved outcomes in the management of RA with earlier diagnosis and advances in treatment, there is still no cure and disease prevention remains an area of intense interest. Studies examining different treatment regimens in varied subsets of patients with pre-clinical RA have been able to delay but not prevent onset of frank RA. In this timely issue of Clinical Rheumatology, Alpziar-Rodriguez D. and Finckh A. highlight the available literature on pre-clinical RA including modifiable risk factors, results of key intervention trials, and discuss whether prevention of RA is on the horizon. We offer additional thoughts on current areas of uncertainty in RA prevention studies, lessons to be learned from prevention trials in other disease states, and future directions to consider.