Both within clinical and wider societal discourses, the term ‘schizophrenia’ has achieved considerable potency as a signifier, privileging particular conceptual frames for understanding and responding to mental distress. However, its status has been subject to instability, as it has lacked indisputable biological correlates that would anchor its place within the canon of medical diagnosis. Informed by a semiotic perspective, this paper focuses on its recent history: how ‘schizophrenia’ has been claimed, appropriated and contested—and how this connects with its earlier history of signification. It also explores how the dominance of this signifier has influenced the ways in which people with the diagnosis may find themselves constructed in their interactions with professionals, family and wider society, and hence how they may come to see themselves. It is argued that, from a point in the 1990s when ‘schizophrenia’ had achieved an almost iconic status, the term is now subject to greater instability, with concerns and challenges being raised from both within and outside psychiatry. On the one hand, this uncertainty has triggered a ‘calls to arms’ from those within the psychiatric establishment who see diagnoses such as ‘schizophrenia’ as crucial to their professional identity and status. On the other hand, this has created spaces for new conversations and alliances between elements within neurology, psychiatry, social work and other professions, and between these and service users. Some of these conversations are casting doubt on the validity and utility of ‘schizophrenia’ as a construct, and are beginning to posit alternative regimes of signification.