Preclinical phases of rheumatoid arthritis (RA) have been described, genetic and environmental risk factors for RA development have been identified, and several biomarkers of RA have been detected long before the clinical onset of the disease; all of which have opened the possibility for preventive interventions. Several studies are currently exploring pharmacological and non-pharmacological interventions to prevent the development of RA. We will review the evidence for prevention of RA and discuss key challenges for preventive interventions, including identification of the adequate target population, the risks of applying potentially harmful and expensive therapies to asymptomatic at-risk individuals, and the importance of taking into account the preferences of individuals at risk regarding preventive treatment options.