GU-rich elements found in pre-mRNA and mRNA transcripts play diverse roles in the control of gene expression by regulating mRNA stability, translation and pre-mRNA processing. Regulatory GU-rich elements are highly conserved throughout evolution, and play major roles in development in diverse species from worms to mammals. The conservation of the GU-rich element allowed it to be identified as a sequence that was enriched in the 3' UTR of human transcripts that exhibited rapid mRNA decay. This element functions, at least in part, as a molecular target for members of the CELF family of RNA-binding proteins, which recruit other components of the cellular posttranscriptional gene regulatory machinery to the transcript. Depending on the context, binding to GU-rich sequences by CELF proteins direct a variety of posttranscriptional regulatory events, including deadenylation, mRNA decay, translation or pre-mRNA processing. Thus, GU-rich elements and CELF proteins serve multiple functions in gene expression regulation and define an important evolutionarily conserved posttranscriptional regulatory network.