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Since resistance to the existing anti\u2010influenza drugs is rising, innovative inhibitors with a different mode of action are urgently needed. The influenza polymerase complex is widely recognized as a key drug target, given its critical role in virus replication and high degree of conservation among influenza A (of human or zoonotic origin) and B viruses. We here review the major progress that has been made in recent years in unravelling the structure and functions of this protein complex, enabling structure\u2010aided drug design toward the core regions of the PA endonuclease, PB1 polymerase, or cap\u2010binding PB2 subunit. Alternatively, inhibitors may target a protein\u2013protein interaction site, a cellular factor involved in viral RNA synthesis, the viral RNA itself, or the nucleoprotein component of the viral ribonucleoprotein. The latest advances made for these diverse pharmacological targets have yielded agents in advanced (i.e., favipiravir and VX\u2010787) or early clinical testing, besides several experimental inhibitors in various stages of development, which are all covered here.<\/jats:p>","DOI":"10.1002\/med.21401","type":"journal-article","created":{"date-parts":[[2016,8,29]],"date-time":"2016-08-29T07:07:33Z","timestamp":1472454453000},"page":"1127-1173","source":"Crossref","is-referenced-by-count":163,"title":["The Influenza Virus Polymerase Complex: An Update on Its Structure, Functions, and Significance for Antiviral Drug Design"],"prefix":"10.1002","volume":"36","author":[{"given":"Annelies","family":"Stevaert","sequence":"first","affiliation":[{"name":"Rega Institute for Medical Research  KU Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lieve","family":"Naesens","sequence":"additional","affiliation":[{"name":"Rega Institute for Medical Research  KU 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