With the increased understanding of the etiology and pathogenesis of rheumatoid arthritis (RA) in recent decades, the notion of disease prevention has arisen. Contemplation of potential preventive strategies must be prefaced by a clear understanding of the rationale for the prevention, as opposed to the treatment, of a disease once established. RA is the most common systemic autoimmune rheumatic disease. The worldwide prevalence is 0.24%, and the lifetime cumulative prevalence approaches 4% in women and 2% in men. RA has severe manifestations leading to chronic pain, impaired quality of life, inability to participate in social and work activities, disability, extra-articular manifestations, and premature mortality. Unfortunately, patients often experience a long duration of symptoms prior to diagnosis, owing to inadequate awareness in the general population, limitations of diagnostic assessments in the early phases of the disease, and a lack of access to rheumatologists globally. Despite the development of novel targeted therapies and substantial improvements in treatment strategies, up to 60% of patients fail to respond adequately to any particular treatment strategy, and 30% of those fail to respond to multiple agents. Therefore, there remains a large proportion of patients who fail to achieve clinical remission and patient-acceptable symptom states. Treatments for RA may be associated with a variety of complications, limiting their sustained usefulness, particularly as related to an increased risk for serious infections. Advancements in therapies have curtailed the previous main driver of mortality, cardiovascular disease, but overall mortality remains elevated in many studies of persons with RA compared to the general population. This commentary reviews the rationale in detail and introduces a clear implication that the ideal strategy would be to develop a means of preventing the onset of clinically apparent joint inflammation among individuals at risk.