Among the different strategies to treat cancer, chemotherapy approaches are the subject of intense research efforts. There is still a high demand for new anticancer drugs exhibiting improved efficiency and selectivity for their use in combined therapy strategies. The high development of molecular and cellular biology tools has made possible the set up of simple in vitro assays, susceptible to automation, thus bringing about the possibility of rapid screening of hundreds of compounds. Chemistry has reacted to this challenge by developing a new technology: combinatorial chemistry. By this procedure large collections of compounds, known as chemical libraries, can be prepared in a rapid and efficient manner. In recent years, combinatorial chemistry has had a great impact on drug discovery programmes addressed to tackling cancer pharmaceutical targets. In this review, the contribution of this technology to the discovery of anticancer drugs that are currently in clinical trials or already in the market is discussed.