New anticancer drugs are increasingly targeted to specific abnormalities in the sequence and expression of a series of genes that operate in a stepwise, combinatorial manner to drive the progression of human cancer. These new-generation molecular therapeutics are expected to be more effective and less toxic than the broadly antiproliferative cytotoxic drugs of the previous era, which still dominate medical treatment of cancer today. Molecular and genomic technologies, particularly the availability of the human genome sequence and the ongoing sequencing of cancer genomes, are now having a major impact on target discovery and validation. Over the past year, the progress of three novel anticancer agents in particular (Herceptin, Glivec and Iressa) has exemplified the potential utility of innovative molecular therapeutics in the clinic. Drugs acting on a range of new genome-based molecular targets are now in preclinical and clinical development.