Research examining the role of social support in patient adjustment to chronic illness has been inconsistent suggesting that patient individual differences play a moderating role. This study examined the hypothesis that the relationship between social support and depressive symptoms would differ as a function of individual differences in trait Agreeableness. Fifty-nine patients with chronic kidney disease were assessed using the Social Provisions Scale, Beck Depression Inventory and NEO-Five-Factor Inventory and were followed-up a year and a half later. After controlling for baseline depressive symptoms and clinical characteristics, regression analyses revealed a significant interaction between social support and Agreeableness predicting change in depressive symptoms. Greater social support among individuals high in Agreeableness was associated with a decrease in depressive symptoms over time, while support had little effect on depression change for individuals low in Agreeableness. These findings underscore the importance of individual difference variables in understanding adjustment to chronic illness.