This article reconstructs the historical development and evolving conceptual architecture of the medical humanities since its emergence as a university subject in the 1960s. Originating in late 1960s US ‘values programmes’, the medical humanities initially deployed critique—philosophical, theological, psychoanalytical and sociological—to interrogate medicine’s epistemic authority, ethical commitments and social power. Yet, from the 1970s onwards, critique operated in implicit conversation with systems theoretical approaches, particularly through the emergence of the biopsychosocial model and early engagements with phenomenology, cybernetics, anthropology and process philosophy. The subsequent rise of narrative methodologies in the 1980s and 1990s consolidated this synthesis by enabling scholars to conceptualise illness experience as an emergent property of complex, open biological and social systems. The article contends that renewing this synthesis is now essential for advancing the field’s transdisciplinary ambitions. Contemporary systems science—encompassing epidemiology, developmental research, social determinants of health and the ‘omics’ disciplines—provides a powerful framework for understanding how social experience becomes biologically embedded across the lifecourse. At the same time, critique remains indispensable for revealing the often-concealed values, power relations and institutional arrangements that shape health and illness. Integrating these orientations would reconnect the medical humanities with its diverse intellectual constituencies, address long-standing fragmentation and enable new engagements with topics such as childhood, inequality, embodiment and lifecourse health. The article concludes by proposing that a concise set of shared systems theoretical concepts could provide the durable conceptual infrastructure needed to sustain ambitious transdisciplinary dialogue across the field.