Background: Assessing and measuring subjective quality of life (QOL) for individuals with profound multiple disabilities (PMD) remain amongst the most difficult challenges for theorists and practitioners in the field. The usual approaches using proxy reporting by familiar others have been demonstrated to be of questionable reliability and validity for persons with PMD. Method: The author's continuing research into understanding the nature of subjective QOL of these individuals has led to the development and evaluating the Life Satisfaction Matrix (LSM), an instrument and procedure for assessing the subjective QOL of these individuals. Results: Qualitative research that provides empirical evidence to support the assumptions underpinning, and face validity of, the LSM is described in this article. Conclusion: Results of the study described herein demonstrate some potential to meet and overcome the above-mentioned challenges to assess and measure the subjective QOL of individuals with PMD.