This article outlines critical issues in the psychiatric assessment of patients presenting with medically unexplained physical symptoms that form the core of the somatoform disorders in current nosologies. The prevalence of these disorders in communities and clinical settings emphasizes that a majority of these patients are primary care service users rather than mental health clients. A brief review of previous studies on the pharmacological management of these syndromes with antidepressants highlights unique features of these disorders that are relevant to the design of double-blind studies. The promising results emerging from some of these studies bring new excitement to the field that may help counter the prevailing therapeutic nihilism, thus attracting new investigators to this area. Finally, several caveats are provided on issues of research design and interpretation for the benefit of those entering this field of research.