Infrared spectroscopy has brought invaluable information about proteins and about the mechanism of action of enzymes. These achievements are difficult to transpose to living organisms as all biological molecules absorb in the mid infrared, with usually a high degree of overlap. Deciphering the contribution of each enzyme is therefore almost impossible. On the other hand, small changes in the infrared spectra of cells induced by environmental conditions or drugs may provide an accurate signature of the metabolic shift experienced by the cell as a response to a change in the growth medium. The present paper aims at reviewing the contribution of infrared spectroscopy to the description of small chemical changes that occur in cells when they are exposed to a drug. In particular, this review will focus on cancer cells and anti-cancer drugs. Results accumulated so far tend to demonstrate that infrared spectroscopy could be a very accurate descriptor of the mode of action of anticancer drugs. If confirmed, such a segmentation of potential drugs according to their "mode of action" will be invaluable for the discovery of new therapeutic molecules. This article is part of a Special Issue entitled: Physiological Enzymology and Protein Functions. (C) 2015 Elsevier B.V. All rights reserved.