The actin cytoskeleton, due to its role in many processes involved in cellular transformation, has long been a sought after anticancer target, yet attempts to develop such compounds have been hampered by unacceptable toxicity. By targeting the other core polymer system of the microfilaments, tropomyosin, it is possible to discriminate between actin filaments required for sarcomeric function and those required for tumor growth. In silico modeling shows the predicted association of the first in class anti-tropomyosin compound, TR100, with the C-terminus of a cancer-associated tropomyosin, Tm5NM1. The interaction between Tm5NM1 and TR100 results in disruption of actin filament organization and death of tumor cells, both in vitro and in vivo. For details, see article by Stehn and colleagues on page 5169.