Conventional tumor therapy is usually based on surgery, radiation and chemotherapy. Treatment with chemotherapeutics is often impeded by dose-limiting toxicities. Therefore, medical scientists sought for tools to improve chemotherapy by directly coupling targeting molecules to cytotoxic substances. This review provides a general overview on the development of targeted drugs designed for tumor therapy. Further carrier-based delivery systems of antitumorigenic drugs will not be described here. The targeting moiety is usually an antibody or a fragment thereof. Growth factors, cytokines and ligands are also used as targeting moiety. The targeting moiety is coupled to the toxic moiety either chemically or both components were combined as fusion proteins. In addition to those targeted molecules containing conventional chemotherapeutics, more sophisticated targeted drugs were developed containing protein toxins, such as diphtheria toxin or Pseudomonas exotoxin. Only a small number of these protein toxins inside tumor cells results in efficient killing of the target cell. Several of these targeted toxins are currently in clinical trials. Another targeting mechanism utilizes the activation of formerly harmless substances in the vicinity of tumor cells. This mechanism is referred to as directed enzyme prodrug therapy.