Peptide or carbohydrate epitopes resulting from aberrant glycosylation, receptors for growth, and differentiation signals have recently been reexamined as candidates for monoclonal antibody-guided therapy. Microdistribution studies have demonstrated the limited penetration of radiolabeled antibodies in tumors. Increased tumor capillary permeability has been obtained by pretreatment with cytokines or by exploitation of monoclonal antibodies against tumor endothelial cells. The use of monoclonal antibodies for combined therapies based on different rationales (multiple monoclonal antibodies, monoclonal antibodies plus cytokines, and monoclonal antibodies plus drugs) is a recent development, and the retargeting of effector cells using hybrid monoclonal antibodies can be considered an extension of this approach. A major driving force in the field of immunotoxins today is represented by progress in protein engineering. Genes encoding various toxins have been cloned, and novel molecules with more desirable biologic properties have been produced. Also, genetic engineering techniques help in overcoming the major limitation in the clinical use of rodent monoclonal antibodies, ie, human antiimmunoglobulin response.