OBJECTIVES: Assessment of the type of instrument used to measure health-related quality of life (HRQoL) in published cancer clinical trials. METHODS: We conducted a keyword search of Medline for cancer clinical trials, published over last five years in English. The inclusion criteria were: adult cancer patients; assessment of HRQoL as an outcome and at least one active treatment arm (chemotherapy, radiotherapy, surgery or some combination). The type of instrument(s) for measuring HRQoL was identified. RESULTS: In total, 789 studies were identified and 42.6% (336) were included. The reasons for exclusion were: disease (9.9%), intervention (69.3%), outcome (12.6%) and study design (8.2%). 42 studies (12.5%) were placebo-controlled while 201 (59.8%) had active comparator treatment arm(s). The most common diagnosis was non-small cell lung cancer (19%). Use of HRQoL instruments was identified in 211 studies. Of these, specific instruments were used in 187 studies; including cancer specific in 182, population specific in 4 and signs and symptoms specific in 1 study. In 103 studies, disease specific instruments (modules) were related to particular type of cancer (studies with breast; colon; brain; prostate; lung; head & neck; and pancreatic cancers). The EORTC and FACT questionnaires were widely used. Generic instruments were used in 23 (6.8%) studies, most common being SF-36 followed by EuroQol group questionnaire. Both generic as well as specific instruments were used in 37 studies. A decrease in the use of specific HRQoL instruments was observed (62% in 2003 vs. 33 % in 2008). Use of specific and generic instruments was similar for trials with active and non-active comparators. CONCLUSIONS: Application of generic HRQoL instruments in cancer clinical trials remains low. Use of specific HRQoL instruments in these trials appears to have declined in the last five years.