Introduction: The Hippo pathway represents a new opportunity for the treatment of cancer. Overexpression of Yes-associated protein (YAP) or transcriptional coactivator with PDZ-binding motif (TAZ) or TEAD has been demonstrated in cancers, and YAP is known to mediate resistance to cancer drugs. Since 2018, the potential of this pathway has been illustrated by numerous articles and patents, and the first drugs entering the clinical trial phase 1. Areas covered: The present review is limited to published patent applications that have disclosed direct small molecule inhibitors of the YAP/TAZ–transcriptional enhanced associate domain (TEAD) interaction. Expert opinion: The YAP/TAZ–TEAD transcriptional complex is a promising target more specifically for the treatment of cancer. In the field of disruptors of the YAP/TAZ–TEAD complex, approximately forty international patents that disclose TEAD transcriptional inhibitors have been filed since 2018. Even though the exact mechanism of action is not always described in the patents, we can divide the drugs into three different categories: (i) the external TEAD ligands (probably interacting at the interface 3 but not fully demonstrated); (ii) the non-covalent TEAD ligands of the palmitate pocket; (iii) the covalent TEAD ligands which bind into the palmitate pocket. The two first molecules in clinical trial phase 1 belong to the family of non-covalent TEAD ligands although their exact structures have not been disclosed. The first selective TEAD1 ligand has also been patented, published and selectivity could be of great interest for personalized medicine.