In the past several years, the relationship between chromatin structure and mRNA processing has been the source of significant investigation across diverse disciplines. Central to these efforts was an unanticipated nonrandom distribution of chromatin marks across transcribed regions of protein-coding genes. In addition to the presence of specific histone modifications at the 5' and 3' ends of genes, exonic DNA was demonstrated to present a distinct chromatin landscape relative to intronic DNA. As splicing in higher eukaryotes predominantly occurs co-transcriptionally, these studies raised the possibility that chromatin modifications may aid the spliceosome in the detection of exons amidst vast stretches of noncoding intronic sequences. Recent investigations have supported a direct role for chromatin in splicing regulation and have suggested an intriguing role for splicing in the establishment of chromatin modifications. Here we will summarize an accumulating body of data that begins to reveal extensive coupling between chromatin structure and pre-mRNA splicing.