A review is given of pathophysiological and etiological theories of negative symptoms. Computer tomography studies and cerebral blood flow studies are briefly reviewed and critically discussed. In addition the neuropathology and neuroendocrinology of schizophrenia in relation to negative symptoms is discussed. Subsequently the role of neuropeptides in relationship with negative symptoms is discussed. The last part of the article contains a discussion of therapeutical strategies in the treatment of negative symptoms. Firstly dopamine agonist strategies are discussed, secondly the role of neuropeptides (vasopressin and TRH) in the treatment of negative symptoms is discussed and a putative therapeutic role for these peptides is suggested.