Splicing requires the accurate recognition of exonic sequences from the surrounding thousands of nucleotides of intronic sequence and is achieved by the coordinate interplay of splicing regulatory elements in genes and the trans-acting RNA and protein molecules to which they bind. Infidelity in this process can have dramatic consequences for protein production, with an errors resulting in mRNA instability or the production of aberrant protein products. It is therefore not surprising that disruptions of splicing processes have been associated with a wide range of diseases, including cancer. This review looks at some of the mechanisms that regulate splicing and how disruption of such mechanisms can contribute to cancer susceptibility and progression.