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This essay challenges fundamental, silo-oriented assumptions about the IS discipline. It shows how work system theory and its extensions form a potential basis for overcoming that silo-orientation and finding and exploiting areas of overlap with other disciplines. Within the IS discipline, this paper shows how WST and extensions provide a basis for thinking differently about fundamental topics including the following: IS as a system-related discipline, system usage, sociotechnical systems, planned and emergent change in systems, system development and systems analysis and design, user participation and IS/IT projects, attaining value from IS and IT, IS success, business/IT alignment, and IS theories and a body of knowledge for IS. This paper also shows directions toward synergies and possible collaborations with other disciplines that build on areas of overlap.