Cancer and its treatment produce multiple symptoms that significantly distress patients and impair function. Symptoms caused by treatment may delay treatment or lead to premature treatment termination, and residual treatment-related symptoms often complicate posttreatment rehabilitation. When treatment is no longer possible, symptom control becomes the focus of cancer care. Patient ratings of symptom severity and impact are important patient-reported outcomes (PROs) in cancer clinical trials and comprise a subset of a larger domain of PROs generally referred to as health-related quality of life (HRQOL). Symptoms rarely occur in isolation; rather, there is now ample evidence that symptoms frequently occur in clusters. The impact of these multiple symptoms upon the patient can be described as "symptom burden," a concept that encompasses both the severity of the symptoms and the patient's perception of the impact of the symptoms. The distress caused by symptoms is a subject of much investigation, and several validated measures of the severity and impact of multiple symptoms are now available. Symptom measures are generally brief, thereby reducing respondent burden, and can be administered repeatedly during a trial to give a relatively fine-grained picture of the patient's status across time. In many instances, information on trial-related changes in symptom burden, or comparison of symptom burden between arms in a clinical trial, may provide sufficient self-report data for clinical trial consumers (patients, clinicians, and regulators) to make treatment choices or to evaluate new therapies, without measuring other HRQOL domains.