Alterations in alternative splicing affect essential biologic processes and are the basis for a number of pathologic conditions, including cancer. In this review we will summarize the evidence supporting the relevance of alternative splicing in lung cancer. An example that illustrates this relevance is the altered balance between Bcl-xL and Bcl-xS, two splice variants of the apoptosis regulator Bcl-x. Splice modifications in cancer-related genes can be associated with modifications either in cis-acting splicing regulatory sequences or in trans-acting splicing factors. In fact, lung tumors show abnormal expression of splicing regulators such as ASF/SF2 or some members of the heterogeneous nuclear ribonucleoprotein family. The potential significance of alternative splicing as a target for lung cancer diagnosis or treatment will also be discussed.