The conjugate cyclopent-en-one chemical group is a special moiety for anticancer drugs. Studies on cyclopentenone prostaglandins, clavulones and other compounds have revealed its mechanism of action and a wide spectrum of intracellular targets, ranging from nuclear factors to mitochondria. The introduction of the cyclopenterione moiety into molecules, such as jasmonates and chalcones, has been shown to boost their anticancer potential. In this work, reviewing pertinent up-to-date literature, we have pointed out potentially effective cyclopentenone-bearing compounds for anticancer clinical research and inspiring relationships for future drug design. In particular, it appears that the addition of cyclopenterione groups to target-orienting molecules, in order to inactivate specific proteins in cells, could be a helpful general strategy for the development of novel therapeutic molecules.