Targeted therapy has replaced the conventional methods of disease management with the advances in recombinant technology and increased understanding of molecular mechanisms of diseases. The immunotoxin strategy for diseases like cancer and a variety of autoimmune disorders has been used successfully in the past since its discovery. Since bacterial, fungal and plant toxins have various limitations like toxicity and immunogenicity, studies on fully humanized immunotoxins have gained attraction recently, which reduced toxicity significantly. Improved methods of antibody engineering have led to the emergence of various new formats of immunotoxins. This review summarizes the target moieties used in immunotoxin constructs in different diseases and describes the recent advances in immunotoxin targeting. © 2012 Elsevier Ltd.