A serious physical illness can become the defining aspect of a person's life. If a belief develops that the illness cannot be resolved, either through medical care or one's own coping efforts, then a person can develop demoralization, which is defined as a pervasive feeling of defeat, hopelessness, and powerlessness. Demoralization involves a depressed mood but differs from a major depressive episode in that demoralization does not exhibit the generalized anhedonia found in major depression. Instead, demoralization has a singular precipitating factor causing the patient's hopelessness, the illness. A patient's demoralization typically remits if some form of hope is restored. The experience of being hospitalized for an illness, which is often overwhelming and difficult for patients, can adversely impact hope and foster or exacerbate demoralization, leading to adverse outcomes. A brief approach to treating demoralization in the hospital environment, emphasizing interpersonal engagement over pharmacological interventions, is described through a case example. The approach is based on the common factors approach to effective psychotherapy and is well suited for use within fast-paced medical settings.