It has long been realized that the presence of tumor-associated antigens offers an excellent opportunity for targeted cancer therapy and hence an improved clinical benefit for cancer patients. Advances in the field of antibody engineering as well as the characterization of toxins, such as diphtheria toxin and Pseudomonas exotoxin A, have enabled the routine construction of recombinant immunotoxins, which we have termed Armed Antibodies. The selective toxicity and mechanism of action of these molecules could potentially provide an excellent clinical alternative to conventional anticancer agents which have many unacceptable side effects. Although considerable clinical success has been achieved using immunotoxin therapy, particularly for B-cell malignancies, the treatment of solid tumors remains highly challenging. To successfully treat solid tumors that are not amenable to local therapy, immunotoxins must be designed to permit repeat systemic administration. This review outlines some of the strategies currently being employed in the design of the Viventia Biotech Inc Armed Antibodies to minimize the development of immunogenicity and to remove the potential for toxicity in non-target tissues.