In the present study, we investigated longitudinally (baseline, 10 weeks, 16 weeks) whether patient personality traits, such as dispositional optimism and mastery, play a role in patients' ability to effectively control the severity of their pain and fatigue in the context of a symptom control intervention among patients with cancer. Two hundred fourteen patients currently undergoing chemotherapy received a baseline interview followed by a 10-week, nurse-assisted symptom control intervention. At 10 weeks, patients received a second interview to assess the effectiveness of the intervention, with a final follow-up interview at 16 weeks. Random effects regression models were used to investigate the effects of mastery and optimism on the severity of pain and fatigue, adjusting for the effects of other important covariates, such as age, gender, cancer site, stage of disease, and comorbidity. Patients who were older, more optimistic, suffered from fewer comorbid conditions, or reported higher levels of mastery tended to report less severe pain, whereas higher levels of mastery and fewer comorbid conditions predicted lower fatigue severity scores. These findings underscore the need for physicians and nurses involved in the care of cancer patients to recognize, encourage, promote, and take advantage of these traits in their patients to help them more effectively manage their cancer care, so that they ultimately can achieve a better quality of life during the sequelae of the cancer experience.