Multicomponent reactions - reactions that combine three or more starting materials in one pot to give a single product that contains essentially all of the atoms of the reactants - offer many exciting opportunities for medicinal chemistry. Their most obvious application is in the drug discovery phase, where they can provide efficient access to large numbers of analogs for lead discovery or optimization. By contrast, the inherent 'greenness' of multicomponent reactions makes them of increasing importance in the sustainable production of pharmaceuticals. We will discuss recent advances in both fields as well as general drivers and barriers for the application of multicomponent reactions in a medicinal chemistry context. ?? 2012 Elsevier Ltd. All rights reserved.