Human cancer has been one of the most difficult and tenacious problems that has defied many therapeutic regimens in the past. In recent years, there has been an explosive growth in our knowledge about molecular cell biology of cancer leading to the development of several molecularly targeted therapies. These therapeutic agents are used specifically for those tumors that are found to be susceptible to such a therapeutic approach. These therapies include a variety of monoclonal antibodies that target cell-surface receptors or, in some cases, their ligands. A second type of targeted therapies consists of small molecules that are designed to inhibit tyrosine kinase activity within the cancer cells. Despite initial optimism, this approach to cancer therapy is proven to be problematic because of inherent cancer heterogeneity and frequent development of drug resistance. The targeted therapies have improved survival time for many cancer patients but have not provided any definitive cures. The treating physicians constantly face the daunting challenge of balancing expected benefit with risk for complications, to achieve the most successful outcome. Still, the results often fall short of expectations. Personalized cancer treatment on the basis of targeted therapies is certainly an achievable goal, but more work is needed to make it a reality.