The purpose of this study was to describe patients' perceptions of the causes, relief, related symptoms, meaning, and suffering secondary to cancer-related fatigue (CRF). In total, 252 patients with breast, lung, colon, and prostate cancers were enrolled in a quasiexperimental study to test the effects of a clinical intervention on reducing barriers to symptom management in ambulatory care. Analysis of data reported in this article was derived from the Piper Fatigue Scale-Revised. Using qualitative research methods and content analysis, written statements related to the impact of CRF were coded using the following themes: patients' perceptions of CRF, causes, relief, related symptoms, meaning, and suffering. Comments were categorized and reviewed for content. Overall, CRF had a significant impact on physical, psychological, social, and spiritual well-being. CRF limited the ability of participants to function, socialize, and participate in enjoyable activities. Emotional issues as a result of CRF were common. The negative impact of CRF on patients' overall well-being alters the meaning and suffering related to the cancer experience. The assessment of personal meaning and suffering related to CRF is an important component of the multidimensional assessment of CRF and will enable nurses to better understand the suffering related to CRF.