Immunologic, metabolic, and increasingly ‘immuno-metabolic’ approaches, are prominent in contemporary psychiatric discourse, yet translation into clinical practice remains variable. In this Feature, we pragmatically ask where signal ends and speculation begins, and what this means for the clinical psychiatrist. Autoimmune encephalitis provides a rare but instructive yardstick in which antibody-based mechanisms map onto distinct neuropsychiatric syndromes and respond to targeted immunotherapy. However, while the broader concept of autoimmune psychosis may extend beyond this tightly defined niche, it remains largely experimental and requires stronger evidence. More broadly applicable concepts, including an immuno-metabolic subtype of depression, are increasingly supported by mechanistic work, with attendant treatment implications, although differentiation from routine holistic care remains less clear. In psychosis and severe mental illness, immune and cardiometabolic dysfunction may contribute to both psychiatric and physical disease burden beyond lifestyle or treatment effects alone. Emerging therapies, including GLP-1-based approaches, may bind these threads together with gains for body and mind, but specific evaluation within psychiatry continues. Overall, our view is that the opportunities are not lost, but for robust translation, there is an ongoing need for precise, incremental research, inter-disciplinary collaboration and rigorous communication of nuance.