The clinical and positive psychology usefulness of quality of life, well-being, and life satisfaction assessments depends on their ability to predict important outcomes and to detect intervention-related change. These issues were explored in the context of a program of instrument validation for the Quality of Life Inventory (QOLI) involving 3,927 clients from various clinical settings. Clinical norms were also generated that supplement existing nationwide norms. The predictive validity of the QOLI and life satisfaction in a university counseling center was supported in terms of its ability to predict academic retention both by itself and in conjunction with cumulative grade point average 1 to 3 years in advance. The QOLI was also found to be sensitive to treatment-related change in two naturalistic clinical settings and samples. The interpretation and intervention utility of measures of quality of life, well-being, and life satisfaction are discussed with respect to clinical and positive psychology research.