Working memory disturbances occur in various psychiatric disorders and play a major role for general cognitive ability in everyday life and thus social integration of the patients. In schizophrenia and bipolar disorder, working memory deficits have been found to be associated with certain genotypes and clinical symptoms. This makes them promising endophenotypes, i.e., mediators between genotype and phenotype. Furthermore recent studies indicate that the identification of selective deficits in working memory may be useful in order to define patient subgroups that are more homogenous with respect to the functional integrity or dysfunction of neural systems underlying working memory subcomponents. This scientific approach may ultimately lead to better understanding of the pathophysiologic mechanisms underlying working memory dysfunctions in psychiatric disorders and may provide clinicians with additional information for diagnostic and therapeutic decisions.