This study examined the influence of optimism on pain medication use in adolescents with sickle cell disease (n=27; 18 females, 9 males). Participants completed a baseline measure of optimism and an average of 100 daily-diary assessments of pain severity and medication use. Results indicated that adolescents who experienced more severe pain used more analgesic and opioid medications. Optimism was a significant moderator of the relation between pain and opioid-medication use. At medium and high levels of optimism, pain was positively related to opioid use, but at low levels of optimism, the same relation was not present, suggesting that more optimistic adolescents are better able to match their medication use to their pain severity. Future research should examine how other psychosocial factors might influence pain medication use in adolescents and adults who experience pain, and clinicians should take into account psychosocial factors when working with pain populations.