Recent advances in the understanding of non-small cell lung cancer (NSCLC) 
biology have revealed a number of 'targetable' genetic alterations that underlie 
cancer growth and survival in specific patients subgroups. The anaplastic 
lymphoma kinase (ALK) gene rearrangement identifies a population of NSCLCs in 
whom dysregulation of ALK-tyrosine kinase (-TK) leads to uncontrolled 
proliferation of cancer cells, thus providing the basis for the therapeutic use 
of ALK-TK inhibitors (-TKIs) in ALK-rearranged (-positive) disease. Crizotinib 
was the first ALK-TKI to undergo clinical development in ALK-positive advanced 
NSCLC, in which it has been shown to greatly outperform the best available 
chemotherapy regimen in either second- or first-line setting. More recently, the 
novel second-generation ALK-TKI ceritinib has been shown to be highly active in 
either crizotinib-pretreated or -naïve population. Nevertheless, as mechanisms 
of resistance to crizotinib and ALK-TKIs in general are being progressively 
elucidated, the treatment landscape of ALK-positive NSCLC is expected to evolve 
rapidly. In the present review we will briefly discuss the current knowledge of 
ALK-positive advanced non-small cell lung cancer. Also, we will touch upon new 
developments on drugs/combination regimens aimed at inhibiting the ALK-TK, in an 
attempt to delineate how treatment of ALK-positive disease may change in the 
next future.