Aberrant activation of signal transducer and activator of transcription (Stat) 3, a member of the STAT family of proteins, is prevalent in numerous human cancers and is now widely recognized as a critical molecular abnormality and a master regulator of tumor processes. Thus, the identification of potent and selective Stat3 inhibitors will have a high commercial potential as anticancer drugs, given the many tumors in which Stat3 is implicated.This review covers the structures and activities of direct inhibitors of Stat3 protein activity described in the patent literature since the research field's inception in 2001. The patents reviewed include peptide and peptidomimetic compounds, small molecules, oligonucleotides and platinum-based Stat3 inhibitors.Readers will gain an understanding of how Stat3 protein function has been inhibited by a wide variety of structurally diverse therapeutic compounds. Readers will learn about which classes of patented Stat3 inhibitors are most advanced toward clinical trials, and will be exposed to the proposed mechanisms of inhibition and scope of their application in treating human cancers.Numerous groups have shown that in vivo administration of inhibitors of activated Stat3 induce human tumor regression in xenograft models. Indeed, the growing number of preclinical studies in numerous cancer types, as well as the first Phase 0 clinical trial of a Stat3 inhibitor, suggest that Stat3 is a valid and exciting therapeutic target for molecular inhibitors.