The identification of peripheral markers of psychiatric illness is important if an improvement in the diagnosis and treatment of various diseases with overlapping symptomatology is desired. There are many disorders that not only have overlapping symptomatology, but also have similar biological disturbances. The functional capability of the neurons involved in the disease processes may be at the crux of the underlying pathology. The platelet intracellular calcium response to neurotransmitter stimulation has previously been used as a peripheral marker of psychiatric illness. This review discusses evidence in support of the extended use of the platelet as a peripheral marker. The use of the platelet intracellular calcium response to neurotransmitter stimulation as a state or trait marker in major depression, the specificity and selectivity of this response, and the possible use of the platelet as a peripheral marker in psychotic disorders such as schizophrenia, mania and psychotic depression are shown. Finally, a proposed mechanism for the association between certain psychiatric disorders and cardiovascular disease is discussed. Copyright © 2001 John Wiley & Sons, Ltd.