Recent studies directed at understanding alternative splicing control have produced an expanding list of regulators that can enhance or silence the use of splice sites by binding to specific sequences. A fine balance in the expression and the combinatorial use of these factors would help to adapt splicing decisions to a variety of situations. Additional levels of control are provided by tightly connecting the activity of alternative splicing factors with other cellular processes such as signal transduction and transcription. Combining classical experiments and high-throughput approaches is now confirming the important contribution of alternative splicing to proteomic diversity while helping to decipher the underlying networks of splicing regulation.