Since the first use of chemotherapy, many efforts were devoted to develop drugs with a specific anticancer activity. Nevertheless, although several approaches to this end were used leading to significant results in cancer treatment, chemotherapy has mainly a palliative effect. The remarkable scientific advances in the knowledge of molecular changes in neoplastic diseases brought to development of new drugs with a specific molecular target. In some cases, this approach against a single molecular target, has been extremely successful, like imatinib in GIST. However, since in most cases tumor growth involves multiple genetic changes, it seems more appropriate to develop multitargeted agents. A successful way to improve target selectivity of anticancer drugs and to better choose patients to treat could be the use phase 0 clinical trials. In the future, the hope is to discover all genetic changes in each cancer patient and to restore the normal function of the cell with the aid of more advanced technologies.