Although it is generally acknowledged that housing is a major issue regarding health in old and very old age, most empirical research still tends to treat the role of the housing environment in a rather superficial manner. The cross-national project Enabling Autonomy, Participation, and Well-Being in Old Age: The Home Environment as a Determinant for Healthy Ageing (ENABLE-AGE) seeks to make a substantial contribution to this shortcoming. The main objective of the project is to examine subjective and objective aspects of housing and their impact on health in very old age, while health is understood mainly in terms of autonomy, participation and well-being. The project involves five European Union member countries, i.e. Sweden (coordinating unit), Germany, the United Kingdom, Latvia and Hungary. The total sample includes 1,918 older adults in the age range of 75-89 years and living in single households. We provide a systematic analysis of major challenges coming with cross-national research in the housing and ageing domain based on the experience of the ENABLE-AGE Project. Treated are: challenges related to sampling and data collection procedures, challenges related to inclusion and exclusion criteria based on housing characteristics, challenges related to differences in housing legislation, norms, and guidelines, challenges related different availability of professional expertise for person-environment assessments, challenges related to valid and reliable person-environment assessments, and challenges related to the interpretation of housing-related findings.