Multi-component reactions (MCRs) constitute a methodology to shorter syntheses of natural products or complex molecules for drug discovery. Due to the large number of accessible compounds, this type of chemistry has become very popular between scientists who are working in the area of combinatorial chemistry. Over the last decade combinatorial chemistry has evolved from the synthesis of great quantity of simple compounds to the parallel synthesis of complex molecules with a widely varied structure. MCRs are ideally suited for this trend, being free of limitations of a traditional multistep synthesis. The close connection and interference of multicomponent reactions and combinatorial chemistry are discussed in this review.