TEAD transcription factors pair with YAP and TAZ to orchestrate various transcriptional programs of cell proliferation and cell death suppression that promote cancer development.The structure of TEAD complexed with YAP/TAZ reveals several possible avenues for pharmacological modulation, making TEAD an attractive therapeutic target.Small molecules that bind to TEAD that abrogate activity are currently being tested in clinical trials.TEAD inhibitors may be effective monotherapies for a subset of cancers driven by the YAP/TAZ–TEAD transcriptional complex.The administration of TEAD inhibitors in combination with other targeted therapies is being investigated to overcome drug resistance. The Hippo signaling pathway inhibits the activity of the oncogenic YAP (Yes-associated protein)/TAZ (transcriptional co-activator with PDZ-binding motif)–TEAD (TEA/ATTS domain) transcriptional complex. In cancers, inactivating mutations in upstream Hippo components and/or enhanced activity of YAP/TAZ and TEAD have been observed. The activity of this transcriptional complex can be effectively inhibited by targeting the TEAD family of transcription factors. The development of TEAD inhibitors has been driven by the discovery that TEAD has druggable hydrophobic pockets, and is currently at the clinical development stage. Three small molecule TEAD inhibitors are currently being tested in Phase I clinical trials. In this review, we highlight the role of TEADs in cancer, discuss various avenues through which TEAD activity can be inhibited, and outline the opportunities for the administration of TEAD inhibitors.