Identifying health-related quality of life concerns is a priority when caring for people with cancer. Specific problem areas such as pain, fatigue, emotional distress, disease- and treatment-related symptoms, as well as physical functioning can be routinely assessed using applications that draw upon item response theory. Item response theory measurement models can improve on the classical approach to health-related quality of life assessment with advantages that include comparison of patients across diverse instruments, flexibility in degree of precision desired, availability of multiple short forms, interval measurement and capability for individual assessment (real-time clinical monitoring) using computerized adaptive testing. This review describes a model of health-related quality of life in oncology and the contribution of item response theory to assessment using that model.