The currently most popular definitions of “borderline” are those of Kernberg, Gunderson and Spitzer (now incorporated into the DSM-III). The Kernberg criteria define a level of function (between “Neurotic” and “Psychotic”); the Gunderson criteria, a more narrowly circumscribed clinical syndrome, phenomenologically distinct from schizophrenia and from the psychoneuroses. The DSM-III criteria are derived from these and other sources and define a broad domain that includes the other usages of “borderline.” Even the narrower definitions of borderline describe a collection of conditions heterogeneous with respect to hereditary, constitutional and psychosocial factors. Genetic, biochemical and clinical research suggests the appropriateness of dividing the borderline domain into a variety of sub-types. The largest proportion of borderline cases are effective (with prominent depressive symptoms; occasionally, with cyclothymic or hypomanic symptoms). Of these, some show strong “endogenous” features, as well as family pedigrees of manic-depressive illness. This category includes many patients with anorexia nervosa or with agoraphobia. In others, the affective symptoms seem more related to severe psychosocial stresses in early life (including physical abuse, parental deprivation, or incest). Smaller proportions within the borderline domain are occupied by schizotypal cases (many with hereditary linkage to core schizophrenia), or by organic cases (including temporal lobe epilepsy, or minimal brain damage, giving rise to the “episodic dyscontrol” syndrome). Biochemical and nerophysiological markers that may be useful in distinguishing among the borderline subtypes include measure of platelet MA O-activity, of dexamethasone suppression, of R.E.M. latency, motion-sickness susceptibility and of average evoked response to photic stimulation. Attention to subtypes is important in considering optimal treatment for borderline patients. Not all respond to analytically-oriented psychotherapy alone. Those with severe affective symptoms often require antidepressant medication or lithium. Affectively ill borderlines usually have a better prognosis than schizotypals. In cases of episodic dyscontrol, anti-epileptic drugs may be useful.