About half of the world's population live in Asia. Mandarin (the official language of China), Hindi and Japanese are among the ten languages spoken by the largest number of primary speakers. The numbers of Tamil and Malay speakers are expected to grow rapidly in the next few decades. Most health-related quality-of-life (HR-QOL) instruments currently used in Asia are translations and/or adaptations of instruments developed in North America and Western Europe. We illustrate and discuss several major issues in the development of HR-QOL instruments for use in Asia. We have seen insufficient quality in translation and semantic equivalence, which is not a uniquely Asian problem. This problem will be alleviated by putting recently proposed guidelines for translation and adaptation of patient-reported outcomes into practice and formally conducting equivalence studies. For copyright or other reasons it is rare to see major adaptations, such as exclusion of a domain in the original instrument or inclusion of a new domain, made to existing instruments. Evidence is limited and mixed as to whether there are differences in the concepts of HR-QOL between Asian and North American/Western European cultures that are important enough to justify such major adaptations, or the development of indigenous instruments, as opposed to the translation/adaptation of existing instruments. There are substantial cultural differences concerning what questions are appropriate to ask and answer. Many HR-QOL instruments are designed for self-completion. This mode of administration is often not feasible in Asia because of low literacy rates and the presence of many different regional languages. Alternative administration methods and analytic strategies that allow for pooling data collected by different modes are needed. The availability of HR-QOL instruments in various Asian countries seems to reflect the status of economic development of the countries rather than their disease burden. For instance, many important HR-QOL instruments are available in Japanese but not in Hindi or Tamil.