Experiments reported over the past several years, including genome-wide microarray approaches, have demonstrated that many eukaryotic RNA-binding proteins (RBPs) associate with multiple messenger RNAs (mRNAs) both in vitro and in vivo. This multi-targeted binding property of RBPs has led to a model of regulated gene expression in eukaryotes that we termed the post-transcriptional operon. This concept was established by an analogy between polycistronic mRNAs that are generated from bacterial operons, and the co-ordinated regulation of multiple monocistronic mRNAs by RBPs. Post-transcriptional operons represent a powerful mechanism to organize and express genetic information as functionally related combinations of monocistronic mRNAs. In fact, much of the diversification of individual proteomes may be determined by the combinatorial properties of post-transcriptional operons. This review examines data supporting the role of post-transcriptional operons and regulons in organizing genetic information and co-ordinating expression of functionally related transcripts from their origins at transcription to their subsequent splicing, export and translation.