STAT3 is activated in most human solid tumors and is involved in the proliferation, angiogenesis, and antiapoptosis of cancer cells. Cryptotanshinone, a major diterpene with tanshinone IIA from Salvia miltiorrhiza Bunge (Danshen), was identified as a STAT3 inhibitor by STAT3-dependent luciferase assay. Although cryptotanshinone was reported to possess antibacterial, anti-inflammatory, and anti-atherosclerosis activity, mechanistic study of cryptotanshinone in biological activity has been poorly understood until recently. In this report, the authors suggest that cryptotanshinone could be an inhibitor of STAT3 but not tanshinone IIA. Translocalization of STAT3 into the nucleus through dimerization was remarkably inhibited by cryptotanshinone but not tanshinone IIA. Cryptotanshinone was mainly located in the cytoplasm along with the STAT3 molecule; however, tanshinone IIA was ubiquitously located in the cytoplasm and nucleus independent to the location of STAT3. Using these data, the authors conclude that cryptotanshinone inhibits Tyr705 phosphorylation via directly binding to STAT3 molecules and thus prevents dimerization of STAT3 molecules. Computational modeling shows that cryptotanshinone could possibly bind to the SH2 domain of STAT3. The cover shows the predicted hydrogen bonds between cryptotanshinone and amino acid residues, including Arg609 and Ile634. For details, see the article by Shin and colleagues on page 193 of this issue.