This review will provide an overview of the progress and current strategies to directly and indirectly target the YAP1/TAZ protein–protein interaction (PPI) with TEAD1–4 across multiple modalities, with focus on recent small molecules able to selectively bind to TEAD, block its autopalmitoylation and inhibit YAP1/TAZ–TEAD-dependent transcription in cancer. The gene discussed is TEAD1; the disease is cancer.