Despite increasing interest in assessing health-related quality of life (HRQoL) in randomized trials in gastrointestinal cancer, there remains uncertainty regarding the added value of this data to clinical decision-making. Reasons for this observation may relate to inadequacies in trial design and reporting, and difficulties in understanding and interpreting HRQoL data in a clinical context. It is essential to design trials to capture the relevant changes in HRQoL and for clinicians to be able to understand and communicate the results to patients. Even if HRQoL data are discussed routinely in clinical consultations, there are challenges in facilitating patients' understanding of such outcomes. A range of methods, including narrative descriptions and graphs, may represent the optimal option to discuss HRQoL data with patients in the context of shared decision-making. This review considers these issues in detail and future areas for applied HRQoL research.