During the past 20 years, targeted therapy based on the understanding of tumor biology has been complementing or even replacing cytotoxic agents that have dominated pharmacotherapy of cancer since the conception of medical oncology. Unfortunately, the fact that targeted therapies with potential to induce cure or at least substantially prolong survival are still not available for many common solid tumors results in skepticism or even nihilism. On the one hand, biomarker research is not keeping pace with the introduction of new agents, while on the other hand, effective drugs are still not available for many potential molecular targets associated with malignant transformation and tumor progression. However, targeted therapies have already transformed the natural history and clinical outcomes not only in patients with rare malignancies like gastrointestinal stromal tumor but also with many common tumors, e.g. breast cancer, malignant melanoma, non-small cell lung cancer or renal cell carcinoma. For further advances, a multidisciplinary effort is indispensible that should, above all, involve the collaboration of medical oncology and laboratory medicine.