Health-related quality of life (HRQoL) has become an important outcome measure in patients with chronic liver disease (CLD). In this article, an overview is given of the most common measurement instruments of HRQoL, determinants of HRQoL in patients with CLD, and current developments in the implementation of routine measurement of HRQoL in daily clinical practice. Well-developed generic instruments of HRQoL are the Short Form-36 (SF-36), the Nottingham Health Profile (NHP) and the Sickness Impact Profile (SIP). Well-developed liver disease-specific HRQoL instruments are the Hepatitis Quality of Life Questionnaire (HQLQ), the Chronic Liver Disease Questionnaire (CLDQ), the Liver Disease Quality Of Life Questionnaire (LDQOL ), and the Liver Disease Symptom Index 2.0 (LDSI 2.0). Commonly used HRQoL measures in cost-effectiveness studies are the Health Utilities Index (HUI), Short Form-6D (SF-6D) and the EuroQol-5D (EQ-5D). HRQoL of patients with chronic liver disease has been shown to be impaired, with patients with hepatitis C showing the worst HRQoL. Disease severity, pruritus, joint pain, abdominal pain, muscle cramps, fatigue, depression and anxiety have been associated with HRQoL in patients with CLD. Recently, studies assessing the feasibility and effectiveness of measuring HRQoL in daily clinical practice have been performed, generally showing positive results regarding the discussion of HRQoL-related topics, but mixed results regarding the added value of actual improvement in HRQoL. Furthermore, logistic and attitudinal barriers seem to impede successful implementation. Nevertheless, given the importance of HRQoL in liver patients, we should persist in measuring and subsequently improving HRQoL in clinical practice.