Yes-associated protein (YAP) and TAZ (WW domain containing transcription regulator 1, or WWTR1) are paralog transcriptional regulators, able to integrate mechanical, metabolic, and signaling inputs to regulate cell growth and differentiation during development and neoplastic progression. YAP and TAZ hold common and distinctive structural features, reflecting only partially overlapping regulatory mechanisms. The two paralogs interact with both shared and specific transcriptional partners and control nonidentical transcriptional programs. Although most of the available literature considers YAP and TAZ as functionally redundant, they play distinctive or even contrasting roles in different contexts. The issue of their divergent roles is currently underexplored but holds fundamental implications for mechanistic and translational studies. Here, we aim to review the available literature on the biological functions of YAP and TAZ, highlighting differential roles that distinguish these two paralogues.