AbstractThe recent development of the analytical techniques offers the unprecedented possibility to study simultaneously concentration of dozens of elements in the same biological matrix sample of 0.5–1.0 g (multielement profiles). The first part of this essay entitled “Think globally… An outline of trace elements in health and disease” aims to introduce the reader to the fascinating field of elements, there importance to our nutrition, their essentiality, deficiency, toxicity and bioavailability to the body and their overall role in health and disease, including the genetic metabolic impairments. In the second part of the essay entitled “… and act locally. The multielement profile of depression” we aimed to show the potential of such a hair multielement profile analysis for the study of human depression in a randomized, double blind, prospective, observational, cross-sectional, clinical, epidemiological, and analytical study. The preliminary results of this ongoing study lead us to put forward the hypothesis that the metabolic origin of depression may be due to some “energostat” failure, probably located in the thalamus, and activated by several essential element deficiencies.