The rise of science in the last 400 years, in the academy and in socio-economic life in the West, has culminated in a crisis in the human endeavor of ‘knowing’. Western policy makers have promoted the upgrading and uptake of science in the name of short-term economic goals by way of downgrading forms of ‘knowing’ that do not demonstrate immediate applicability to problems inherent in capitalism (Cobley P, Am J Semiotics, 30(3–4):205–228, 2014). Thus, pursuits such as those associated with the arts and humanities have been marginalized for their supposed failure to conform to standards of applicable knowledge, while mathematics and other ‘theoretical’ disciplines are increasingly yoked to the demands of producing new technologies. Partly in response to this crisis, the last two decades has seen the growth of a considerable amount of theorizing and a vibrant field concerned with ‘practice as research’ (PaR) or ‘practice-led research’. This field treats artistic practices as forms of ‘knowing’ which can complement, supplement, enrich and provide alternatives to scientific ‘knowing’ without being subordinate to it. Arising from early observations on reflective practice (Schön DA, The reflective practitioner: how professionals think in action. Basic Books, New York, 1984; Kemmis S, ‘Action research and the politics of reflection’ In: Boud DR. et al. (eds) Reflection: turning experience into learning. Falmer Press, Falmer: pp 139–163, 1985; Boud DR, et al. (eds) Reflection: turning experience into learning. Falmer Press, Falmer, 1985), work on PaR and practice-led research, has gone some way to establishing a more explicit understanding of practice in the arts and elsewhere as fixtures in the academy, through, for example, validating practice-based PhDs. To a great extent, the work in this area during the last 20 years – in relation to practice in general (Schatzki K-C, von Savigny E (Eds.) The practice turn in contemporary theory. London: Routledge, 2001; Borgdorff H, In Dutch J Music Ther, 12(1):1–17 (originally published in 2006 in the Sensuous Knowledge series, 02 [Bergen: Bergen National Academy of the Arts]), 2007; Smith H, Dean RT (eds) Practice-led research, research-led practice in the creative arts. Edinburgh University Press, Edinburgh, 2009a; Barrett E, Bolt B (eds) Practice as research: Approaches to creative arts enquiry. I. B. Tauris, London/New York, 2007) and in relation to specific practices such as creative writing, performance, dance, experiment, community arts, etc. – exemplifies a philosophy of knowing. Yet, in doing so, this work struggles with various theoretical perspectives that have usually arisen out of traditional conceptions of disciplinary boundaries. Possibly the most sympathetic philosophy of knowing in relation to the cause of PaR and practice-led research – a perspective that is absent from the literature on the topic - is offered by cybersemiotics (Brier S, Cybersemiotics: Why information is not enough!. University of Toronto Press, Toronto/London, 2008; Brier S, Entropy 12: 1902–1920. https://doi.org/10.3390/e12081902, 2010). As cybersemiotics has long contended, the emphasis on knowing as an ‘engineering problem’, addressing a “syntactic-structural aspect in cognition, thought, and communication”, has led to “a decreased interest in the cultural-societal and historical dimensions of the meaning of human cognition and communication” rendering “the social sciences, humanities, and arts much less important in finding the processes of the construction of meaning than most researchers within these domains themselves believe” (Brier S, Cybersemiotics: Why information is not enough!. University of Toronto Press, Toronto/London, 2008, p. 56–57). Cybersemiotics proposes a thorough transdisciplinary approach to this problem, comprising a marriage of evolutionary perspectives on cognition and biology with a formulation on self-referring autopoietic observership derived from semiotics and second-order cybernetics. This paper introduces a cybersemiotic perspective on the capacity of arts and other practice for knowing, suggesting pathways for developing PaR and practice-led research, as well as reviewing the literature of this new configuration in cybersemiotic terms.