The current state of the biological approaches to psychopathology is chaotic; no markers have been accepted despite the fact that dozens have resulted in promising, if not dramatic, results. Under the current requirement for diagnostic specificity, we suspect that no marker will ever be accepted. As we have suggested, research using alternative views of diagnosis, vulnerability, and heterogeneity may hold greater promise for the 1980s. Psychiatric diagnosis will be metamorphosized by research shifting the biological marker from dependent variable to independent criterion. New diagnostic categories may be created around marker rather than symptom variables. This could lead to new labels for old familiar and perhaps pejorative categories. Similarly, treatment would be aimed at understanding specific brain dysfunction of each distressed individual. This would be done with laboratory tests of neurotransmitter, neuroendocrine, and metabolic function. Psychophysiological and psychological testing would complete such an evaluation. The response would be an individualized combination of somatic and nonsomatic treatment. At the present time, several markers are just at the edge between research tools and clinical usefulness (see review by Uytdenhoef et al 1982); new strategies may bring one or more into clinical practice. Finally, the use of markers in relatives or even the general population will open new opportunities for prevention in vulnerable individuals.