This work focuses of the concept of knowledge as instrument for inquiring into organization and information systems. For this proposal a threefold classification of this concept has been introduced: the individual sphere (the knowledge that is within each subject in the form of skills, values and beliefs), the organizational sphere (procedures, routines, roles and technology) and the interorganizational sphere (opportunities, obligations, utilities and facilities that characterize the environment in which companies do business) of knowledge. Through this classification, a number of theoretical approaches are going to be taken into examination to see, respectively, which sphere of knowledge they cover. Therefore it will emerge that one approach can delineate in detail the interorganizational sphere of knowledge having some limits to render the individual sphere and vice-versa. The examination of organizations and information systems using this concept exhibits these methodological features: a methodology that permits the inspection in an organic way of the different aspects that characterize organizations and information systems; a methodology that evaluates the different theoretical approaches and a methodology that manages the data and information at our disposal. The latter can be directly assigned to one of the three spheres and then analysed according to an appropriate theoretical approach.