Hopefulness is a positive psychological construct comprised of cognitive, emotional, motivational, and behavioral components, and which emphasizes goal identification and attainment. Previous research indicates hope is ideally suited for health promotion, symptom management, and recovery in persons with chronic illness, via its beneficial impact on psychological and physiological processes, including psychosocial and immune functioning. Across illness groups, including persons with multiple sclerosis, cardiac disease, and HIV/AIDS, hope is associated with less stress, pain, and impairment, and with greater treatment adherence, and enhanced coping and well-being. We confirmed this pattern of findings in samples of primary care patients, and persons with cancer and fibromyalgia. Although rigorous, prospective research is needed to better understand the hope–illness linkage, our findings and the extant literature have important implications for treatment. Therapeutically promoting hope can reduce pain, fatigue, and stress, and improve general health, psychopathology, inflammation, and quality of life, in persons with chronic illness.