The present article retraces the way in which, over the years, I have developed a post-humanistic approach to social practice on the basis of an Actor-Network sensibility and the way in which practice theory appeared in the literature on learning and knowing in organizations. From this background, I propose an epistemology of practice grounded on relationality, multiplicity, and transformation, and I approach practice as an empirical phenomenon from the perspective of knowing as an activity situated in working and organizing. From this point of view the central interest in practice theories becomes practice as a collective and knowledgeable doing.