A number of Meso-American artifacts which appear to depict subjects presenting severe depressive episodes have been identified, showing that concern with depressive disorders is not a recent phenomenon. Atypical presentations of depression in modern Mexico are characterized by a high degree of somatization, perhaps to avoid the stigma of “mental disorders”. Other characteristics are mood reactivity, substantial anxiety, phobias and the reversed vegetative manifestations. There is a high comorbidity with panic disorder and with bipolar depression. Nosological terminology is not fully standardized, and commonly encountered diagnoses include “neurasthenia”, “neurotic depression”, “mixed depression”, “resistant depression”, etc. Treatment involves a variety of modalities, including TCAs, MAOIs, and anxiolytics, together with a number of drug combinations; open trials are underway with newer agents such as SAMe, SSRIs and the RIMAs.