A cancer diagnosis often affects people’s perceptions of their quality of life (QOL). Improvements to QOL during and after treatment are valued as indicators of success, in tandem with reductions in symptoms and side effects. Insights into how cancer patients assess different aspects of their lives can be more rapidly and comprehensively assessed by a well-designed questionnaire than a time-pressured appointment. A printed profile of scores allows a patient to communicate their perceptions to their clinician and inspect the results themselves. These data can also be the basis for drawing up a mutually agreed treatment plan. While QOL questionnaires assessing symptom intensity and bothersome side effects are well established for use in oncology, they are now more likely to be accompanied by a generic assessment like the WHOQOL that assesses other potentially important QOL dimensions like perceptions of social support, access to health care, financial resources, meaning and purpose in life, and sex life, which may also need to be improved during cancer treatments or afterward. Generic QOL instruments are designed for almost all sick and healthy populations. Their use enables QOL scores for different cancers, or different treatments and interventions to be compared using the same generic measure. Cancer can also be compared with other disease groups, to underpin policy decisions during annual budgeting. Here we review the development and application of the WHOQOL suite of instruments over 25 years, with a particular focus on the QOL of people with cancer.