The catch 22 situation in psychiatry is that for precise diagnostic categories/criteria, we need precise investigative tests, and for precise investigative tests, we need precise diagnostic criteria/categories; and precision in both diagnostics and investigative tests is nonexistent at present. The effort to establish clarity often results in a fresh maze of evidence. In finding the way forward, it is tempting to abandon the scientific method, but that is not possible, since we deal with real human psychopathology, not just concepts to speculate over. Search for clear-cut definitions/diagnostic criteria in psychiatry must be relentless. There is a greater need to be ruthless and blunt in this, rather than being accommodative of diverse opinions. Investigative tests – psychological, serum, CSF, or neuroimaging - are only corroborative at present; they need to become definitive.Medicalisation appears most prominent in psychiatry; so, diagnostic proliferation and fuzziness appear inevitable. And yet, the established diagnostic entities need to forward greater and conclusive precision. Also, the need for clarity and precision must outweigh pandering to and mollifying diverse interests, moreso in the upcoming revision of diagnostic manuals. This is specially because the DSM-5, being an Association manual, may need to accommodate powerful member lobbies; and ICD-11 may similarly need to cater to diverse country lobbies.Finding precise biological correlates of psychiatric phenomena, whether through neuroimaging, molecular neurobiology and/or neurogenomics, is the right way forward. It is in the 1.5-kg structure in the cranium that all secrets of psychiatric conditions lie. Social forces, behavioural modification, psychosocial restructuring, study of intrapsychic processes, and philosophical insights are not to be discounted, but they are supplementary to the primary goal – studying and deciphering those brain processes that result in psychiatric malfunction.Experimental breakthroughs, both in psychiatric aetiology and therapeutics, will come mainly from biology and its adjunct, psychopharmacology; while supplementary and complementary breakthroughs will come from the psychosocial, cognitive and behavioural approaches; the support base will come from phenomenology, epidemiology, nosology and diagnostics; while insights and leads can hopefully come from many fields, especially the psychosocial, the behavioural, the cognitive and the philosophical.Major energies must now be marshalled towards finding biomarkers and deciphering the precise phenotype–genotype–endophenotype axis of psychiatric disorders. Energies also need to be focussed on unravelling those critical processes in the brain that tip the scale towards psychiatric disorders. At how those critical processes are set into motion by forces de novo, in utero, in the genes and their expression, by the environment's psychopathological social forces – stress, peer pressure, poverty, deprivation, alienation, malnutrition, discrimination of various types (caste, gender, race, etc.), mass conflicts (war, terror attacks, etc.), disasters (natural and man-made), religious/ideological fascism – or social institutions like marriage, family, work place, political governance, etc.Ultimately, we must decipher how the brain goes into malfunction when such varied forces impinge on it, which precise cortical areas and neuronal cellular and molecular processes are involved in such malfunction and its manifestation, as also which of these are involved when malfunction ceases and health is restored, and the psychosocial processes and institutions which aid such health restoration, as also those which promote well-being and help in primary prevention.Emphasis on the brain and its intimate neurological and molecular mechanisms will not impinge on, or nullify, importance of the ‘mind,’ wherein subtle and gross brain functions in the form of behaviour, thought and emotions in all their ramifications will continue to be the focus of psychological, cognitive, sociological, psychopharmacological, behavioural and philosophical research. Progress in brain research must move in tandem with progress in ‘mind’ research.