Fatigue is a subjective, unpleasant, potentially disabling symptom rooted in physiological, psychological, and behavioral causes. People living with human immunodeficiency virus (HIV) are a population highly affected by fatigue because of risk factors associated with HIV infection, treatment, and psychosocial disease burden. People with HIV are living longer and are facing the challenge of a longer disease trajectory. Palliative nurses with expertise in symptommanagement can play a crucial role in helping people with HIV to engage in health behaviors that prevent or mitigate fatigue. In this article, the authors present a definition and overview of fatigue, describe the problem of fatigue in people living with HIV, and present a case study that illustrates the role of the palliative nurse in helping a person with HIV to cope with fatigue.