Several decades of cancer research have revealed a pivotal role for tyrosine 
kinases as key regulators of signaling pathways, controlling cell growth and 
differentiation. Deregulation of tyrosine kinase-mediated signaling occurs 
frequently in cancer and is believed to drive the initiation and progression of 
disease. Chromosomal rearrangements involving the tyrosine kinase anaplastic 
lymphoma kinase (ALK) occur in a variety of human malignancies including 
non-small cell lung cancer (NSCLC), anaplastic large cell lymphomas, and 
inflammatory myofibroblastic tumors. The aberrant activation of ALK signaling 
leads to "oncogene addiction" and marked sensitivity to ALK inhibitors such as 
crizotinib (PF-02341066). This review focuses on ALK rearrangements in NSCLC, 
starting with the discovery of the EML4-ALK fusion oncogene, and culminating in 
the recent validation of ALK as a therapeutic target in patients with 
ALK-rearranged NSCLC. Current efforts seek to expand the role of ALK kinase 
inhibition in lung and other cancers and to address the molecular basis for the 
development of resistance.