Multiple chemical sensitivity (MCS) is a controversial disorder of uncertain etiology, characterized by recurrent symptoms referable to multiple organ systems, occurring as a response to chemically unrelated compounds at doses far below those established to cause harmful effects in the general population. The fundamental question is whether the MCS is primarily a toxicodynamic phenomenon (a pathological interaction between a chemical agent and organ systems, possibly acting through a mechanism different from those known in toxicology) or a psychogenic disorder (an emotional reaction to perceived toxic agents). This paper presents some recent theories of etiopathogenesis of the MCS discussing the role of immunological, inflammatory, metabolic, psychophysiologic, and neurochemical mechanisms, as well as the role of neural sensitization in the etiology of the disorder. The paper foregrounds the complex relation between psychiatric disorders and social factors, on one hand, and the MCS on the other. A particular emphasis is put on the relevance of the MCS research for clinical practice, public health, and regulatory decisions.