Until recently, cancer therapy was based on three modalities: surgery, radiotherapy, and cytostatic chemotherapy. In most instances treatment of solid tumors was a surgical domain. For patients with incomplete resection or relapse after surgery, radiotherapy and chemotherapy usually offered only partial response and mostly of limited duration. By the mid-1990s visions of antibody-based therapies, vaccination strategies, and even gene-specific therapies existed but seemed far from clinical practice. United States Federal Drug Administration approval of the humanized antibody rituximab (1997) and the tyrosine kinase inhibitor imatinib (2001) has changed perceptions of oncologic treatment. These drugs turned visions into reality and led the pharmaceutical industry, clinicians, and patients to new perspectives. This article gives an overview of the development of this fourth modality in cancer therapy, so-called targeted therapy.