Quality of life is used increasingly as a primary and secondary endpoint of clinical investigations of new therapies. Quality of life information may be especially useful for the assessment of cancer treatments, where increases in survival may be accompanied by detrimental side effects. The recognition of the importance of quality of life has led to the recent proliferation of cancer specific quality of life instruments. As more is understood about the heterogeneity of patient populations, however, we must assess how culturally defined factors may impact patient quality of life and its assessment. Quality of life instruments are diverse, ranging from those focusing on objective measures of functionality to those assessing subjective measures of patient preferences for their current health state. These instruments have been developed for use in the general population and for disease-specific populations. Assessment of the appropriateness of potential quality of life instruments in specific clinical settings, in addition to understanding the cultural diversity of the clinical population being studied, will guide the researcher in the choice of an appropriate quality of life instrument for cancer clinical trials.