Targeting of toxic compounds to cells has been touted as a promising therapeutic approach to treat diseases such as cancer. The initial excitement gave way to a more sober view, however, as the targeted toxins failed to live up to their promise once tested in patients. Youle and colleagues now report an approach that uses an engineered form of the human body's own RNase protein (see pp. 227 and 265). These workers engineered the protein to target it to cancer cells and at the same time rendered it insensitive to the cytosolic ribonuclease inhibitor that normally limits its activity in cells. This stealthy feat of protein engineering resulted in a targeted therapeutic toxin 5,000 times more toxic to cancer cells than the normal RNase.