INTRODUCTION: Quality of Life (QoL) assessment has become a vital part of international clinical trials. This has made it necessary to produce cross-culturally valid instruments to make comparisons of health status outcomes and pool data across countries. The SLICE/LIFE questionnaire is a 11-item instrument developed in US English to measure the impact of psychological disorders on patients' lives. Prior to use in an international trial including patients with bipolar disorders, the original questionnaire underwent linguistic validation in 16 languages. METHODS: This process involved the recruitment of a QoL specialist in each country. Two forward translations were produced by two native target language speakers, fluent in English. These were reconciled and backtranslated into English. The clarity and appropriateness of the wording were tested in a sample target population, compared and internationally harmonized. The developers clarified concepts underlying problematic items. RESULTS: This process gave rise to linguistic and cultural issues. These included finding a suitable equivalent for the notion of "impairment" for which different syntactic structures were adopted in most translations. Furthermore, it was impossible to maintain a literal translation of the term "partner" in conjunction with "someone you live with" as the interpretation of the two concepts differed across countries. Finally, as in most cultures it would have sounded insulting to employ a literal translation of "mental illness" in the context of a questionnaire, more adapted expressions needed to be found. CONCLUSION: A rigorous methodology ensured conceptual equivalence and acceptability of the translations. Psychometric testing will be conducted to ensure reliability and validity of each translation, appropriateness of the questionnaire in each country, and comparability of data across countries.