Like other members of the signal transducer and activator of transcription (STAT) family of proteins, STAT6 has a dual role as signaling molecule and transcription factor. STAT6 is tightly connected to IL-4 and IL-13 signaling, and plays a key role in TH2 polarization of the immune system, as studies on knockout mice have illustrated impressively. The last 5 years have yielded many new insights into various aspects of STAT6 signaling. While the canonical view of STAT6 activation and biology remains largely unaltered, significant progress has been made in the identification of factors involved in STAT6 activity and STAT6-mediated gene regulation. About 35 different STAT6 target genes have been identified to date, many of which are involved in TH2-associated processes. This review summarizes the existing data on STAT6. Older landmark studies are discussed, as well as surprising recent additions, like hints on inactive STAT6 dimers and the discovery of novel STAT6 isoforms. There is a particular focus on molecular aspects such as modifications of STAT6 and regulation of STAT6-dependent genes, since studies on these aspects have been particularly fruitful during the last few years.