OBJECTIVES: The Multiple Sclerosis International Quality of Life (MusiQoL) questionnaire is a self-administered, measure designed to evaluate the quality of life of patients with multiple sclerosis (MS). The MusiQoL was co-developed in 14 countries. It is composed of 31 items describing nine dimensions (activity of daily living, psychological well-being, symptoms, relationships with friends, relationships with family, relationships with health care system, sentimental and sexual life, coping, and rejection). The objective of this study is to present the challenges faced during the translation of the MusiQoL in 57 additional languages representing seven language families. METHODS: In each country, the translation process (linguistic validation) was conducted by a linguistic expert, using either the standard forward/backward methodology or the adjusted process, including cognitive interviews with six patients. The basis for discussion was the concept list developed in collaboration with the authors. RESULTS: Semantic and cultural issues emerged during the process. First, item 6 (had difficulty with your occupational activities: e.g., integration, interruption, limitation…?) could not be literally translated in most of the countries. Patients had difficulties understanding the words “integration, interruption, limitation.” The periphrasis and examples suggested in the concept list had to be used in most cases. Examples of solutions will be provided. Second, activities (e.g., shopping, going out to a movie, Do-It-Yourself, gardening) described in the original had to be adapted to the religious and social context of the target countries. For instance, “going out to a movie” had to be replaced by “going to an amusement park” in Saudi Arabia, since cinemas are forbidden for religious reasons. Other examples will be presented. CONCLUSIONS: The initial simultaneous development of the MusiQoL in 14 countries minimized the challenges faced during the translation in 57 additional languages. The collaboration with the developers and the patients’ interviews helped to solve the major issues.