The authors examined the relationship between depressive symptoms, smoking, problem drinking, and quality of life among 973 head and neck cancer patients who were surveyed and had their charts audited. Forty-six percent screened positive for depressive symptoms, 30% smoked, and 16% screened positive for problem drinking. Controlling for clinical and demographic variables, linear-regression analyses showed that depressive symptoms had a strong negative association with all 12 quality-of-life scales; smoking had a negative association on all but one of the quality-of-life scales; and problem drinking was not associated with any of the quality-of-life scales. Interventions targeting depression, smoking, and problem drinking need to be integrated into oncology clinics.