Current environmental problems increasingly call for research - as well as education - which crosses the traditional divides between well-established scientific disciplines and between natural science, technical sciences, social sciences and the humanities. This paper addresses the issue of what interdisciplinarity, at the interface between the natural and human sciences, entails and the theoretical problems and obstacles interdisciplinarity encounters. A number of attempts to institutionalize interdisciplinarity, at the Human-Environment interface, in 'fields of study' or even 'disciplines', are briefly discussed, including Geography, Human Ecology, Environmental Studies, Environmental Management, Ecological Economics, Sustainability Science and Earth System Science. Key problems of carrying out interdisciplinary research are identified, including differences of both ontological, epistemological and methodological nature. Particular attention is paid to differences between disciplines in the way they 'explain' and 'interpret' phenomena and regularities, and in 'world-views', pre-analytic assumptions and in time scales.