The significance of evaluations of stressors in rheumatoid arthritis (RA) patients was investigated from the perspective of holistic medicine. The subjects were RA patients treated in the rheumatology outpatient clinic. They included 30 patients from 1987, 30 from 2002, and 137 from 2009. To investigate the specific causes of stress, the patients were asked the question, "What do you feel is your strongest stressor?" The same patients also underwent psychological testing and was examined the disease activity. Pain was the strongest stressor in RA patients in 1987, 2002, and 2009. However, the percentage of patients citing pain as their major stressor was decreasing with each year. CRP was significantly lower in 2009 than in 2002. CRP was also significantly lower in patients who used biologics than in patients who did not. In 2009, DAS28-CRP was significantly higher in patients whose largest stressor was pain than in patients whose largest stressor was another factor. In 2009, the values for both state anxiety and trait anxiety were significantly higher in patients who said that they had stressors than in those who said they did not. The strongest stressor in RA patients was pain. However, the percentage decreased over the years with lower disease activity from advances in therapeutic agents such as biologics. Meanwhile, stressors other than pain were the same or somewhat increased, and they were related to anxiety or depression. Understanding stressors in RA is thus important in treating RA patients.