Patient-reported outcomes are recognized as essential for the evaluation of medical and public health interventions. Over the last 50 years, health-related quality of life (HRQoL) research has grown exponentially from 0 to more than 17,000 papers published annually. We provide an overview of generic HRQoL measures used widely in epidemiological studies, health services research, population studies, and randomized clinical trials [e.g., Medical Outcomes Study SF-36 and the Patient-Reported Outcomes Measurement Information System (PROMIS)-29]. In addition, we review methods used for economic analysis and calculation of the quality-adjusted life year (QALY). These include the EQ-5D, the Health Utilities Index (HUI), the self-administered Quality of Well-being Scale (QWB-SA), and the Health and Activities Limitation Index (HALex). Furthermore, we consider hybrid measures such as the SF-6D and the PROMIS-Preference (PROPr). The plethora of HRQoL measures has impeded cumulative science because incomparable measures have been used in different studies. Linking among different measures and consensus on standard HRQoL measurement should now be prioritized. In addition, enabling widespread access to common measures is necessary to accelerate future progress.