In this article, we will focus on how preferences and utilities are measured, including the strengths and limitations of various approaches, discuss their use in estimating quality-adjusted life-years (QALYs) and make some recommendations for further research. Preferences are either measured using direct (visual analog scale, time trade-off or standard gamble) or indirect methods. The most commonly used generic indirect measures include the Quality of Well-Being scale, EuroQol-5 Dimension, Health Utilities Index and Short Form-6 Dimension. Disease-specific preference measures are increasingly being developed and applied in studies as more sensitive measures of health status. Preference-based measures and QALY measurement need to be enhanced, and additional research is needed to improve scientific methods for estimating preferences for health assessment. Given the increased focus on comparative effectiveness research, QALYs have the potential for helping researchers, clinicians, health policy-makers and patients to understand the relative effectiveness of alternative interventions for treating medical conditions.