Although numerous measures have been developed for the evaluation of health-related quality of life (HRQoL), strategies for identifying meaningful intra-individual change in these measures have not kept pace with instrument development. As a result, clinical trial researchers, quality assurance assessment teams and practising clinicians are without established standards to evaluate individual patient change in HRQoL measures as improved, stable or declined. This article reviews and critiques the methods that have been applied to establish intra-individual HRQoL change standards. These methods include within-person and between-persons anchor-based studies, as well as distribution-based techniques using the effect size, the standard error of measurement, the mean squared error or individual slope coefficients derived from hierarchical linear modelling. Practical approaches to improving and advancing HRQoL change evaluations that enhance the interpretation of intra-individual change are provided. Two future methodological challenges in this area of HRQoL research are examined: (1) the development of individual change standards for generic HRQoL measures; and (2) the incorporation of individual clinical assessments into the process for establishing significant intra-individual change standards.