This report reviews 21 recent empirical investigations of the relationship between personality pathology and patient response to somatic treatments for major depression. The literature review reveals robust evidence, on the basis of 14 studies employing DSM‐III criteria for the diagnosis of Axis II personality disorders, that Axis II co‐morbidity predicts negative outcomes, both acute and longer‐term, among both inpatients and outpatients receiving pharmacological treatment for depression; seven studies utilizing non‐DSM III measures of personality pathology also generally corroborate this finding. A meta‐analysis of three reported studies of ECT response also reveals significantly poorer outcomes among personality disordered inpatients receiving ECT. There is insufficient evidence to conclude whether or not specific Axis II disorders, or clusters of disorders, are associated with particularly poor acute somatic treatment response, though there is modest evidence that Cluster C disorders are differentially predictive of poor acute response among outpatients. Dimensional scores reflecting the total number of Axis II criteria met by the patient are significantly negatively correlated with acute and long‐term somatic treatment response. Numerous methodological difficulties inherent in the study of personality and treatment outcome are addressed. Specific methodological recommendations include the use of structured interviews for personality assessment, the use of continuous rather than dichotomous measures of personality pathology, controlling statistically for differences in initial depression severity among subjects, and ensuring homogeneity of somatic treatment within each evaluated treatment condition. Several possible explanations of the observed relationship between personality pathology and somatic treatment response are also explored. Depression 2:200–217 (1994/1995). © 1995 Wiley‐Liss, Inc.