The Ccr4-Not complex is a global regulator of gene expression that is conserved from yeast to human. It is a large complex that in the yeast Saccharmyces cerevisiae exists in two prominent forms of 0.9–1.2 and 1.9–2 MDa, and consists of at least nine core subunits: the five Not proteins (Not1p to Not5p), Caf1p, Caf40p, Caf130p and Ccr4p. It was initially described to be a global regulator of transcription, based upon the observation that the levels of many transcripts were increased or decreased in mutants. However, the recent finding that Caf1p and Ccr4p encode the major yeast deadenylase has suggested that this complex may additionally play a role in RNA degradation. In this review, the events that led to the identification of the Ccr4-Not complex are described and the elements that clearly demonstrate that the Ccr4-Not complex regulates many different cellular functions are discussed, including RNA degradation and transcription initiation. The evidence points to a role for the Ccr4-Not complex as a regulatory platform that senses nutrient levels and stress.