One of the fundamental principles of pharmacology is that most drugs have side effects. Although considerable attention is paid to detrimental side effects, drugs can also have beneficial side effects. Given the time and expense of drug development, it would be particularly exciting if a systematic method could be applied to reveal all of the activities, including the unappreciated actions, of a potential drug. The present study takes the first step along this path. An activity-based proteomics strategy was used to simultaneously identify targets and screen for their inhibitors in prostate cancer. Orlistat, a Food and Drug Administration-approved drug used for treating obesity, was included in this screen. Surprisingly, we find a new molecular target and a potential new application for Orlistat. Orlistat is a novel inhibitor of the thioesterase domain of fatty acid synthase, an enzyme strongly linked to tumor progression. By virtue of its ability to inhibit fatty acid synthase, Orlistat halts tumor cell proliferation, induces tumor cell apoptosis, and inhibits the growth of PC-3 tumors in nude mice.