Spirituality is an important though often neglected aspect of pain in patients with human immunodeficiency virus (HIV) and/or cancer, for both patients and nurses. The spiritual domain involves: (1) meaning, (2) hope and (3) love and relatedness. The author examines spiritual aspects of pain in persons with HIV and/or cancer, as supported by the literature. Understanding spiritual aspects of pain carries implications for nursing. One of these implications is that it is important for the nurse to be closer to his/her own spirit in order to be there for the patient in pain. Other nursing implications include spiritual assessment and interventions, such as presence, attentive listening, acceptance and judicious self-disclosure, for promoting comfort and diminishing pain.