The main aim of this study was to investigate whether defensive pessimism in interaction with trait anxiety was associated with better adaptation to chronic pain operationalized as greater well-being, a higher level of daily functioning, and less disability. The sample comprised 276 patients with chronic musculoskeletal pain. Three hierarchical stepwise regression analyses were performed. Statistically significant associations were found between defensive pessimism in interaction with trait anxiety and well-being, and between dispositional optimism and better functioning and greater well-being. The central role of dispositional optimism in adaptation to chronic pain is discussed. We speculate that defensive pessimism and optimism could coexist in the same individual, understanding defensive pessimism as a cognitive strategy aimed at managing a specific task, and dispositional optimism as generalized positive expectations. The clinical implications of these findings are discussed.