Constitutive and alternative splicing events are regulated, in higher eukaryotes, by the action of multiple weak cis-acting elements and trans-acting factors. In particular, several evidences have suggested that silencers might have a fundamental role in preventing pseudoexon inclusion in mature transcripts and in defining constitutive exons by suppressing nearby decoy splice sites. Moreover, silencer elements allow the recruitment of regulatory factors to alternatively spliced exons, therefore participating in the modulation of alternative splicing pathways. Here we focus on splicing repression mechanisms in mammals, with particular concern to both exonic and intronic silencer elements, secondary structure formation and role in human genetic disease.Recently, in addition to the availability of a growing number of sequence elements deriving from the analysis of individual regulated exons, approaches have been developed that allowed the systematic identification of splicing silencers. These methods and are briefly described, as well as the motifs they retrieved, and summary of silenced exons is provided.