In 2007, the rearrangement of anaplastic lymphoma kinase (ALK) was identified to 
be associated with the pathogenesis of a subset of patients with non-small-cell 
lung cancer (NSCLC). Surprisingly, approximately 4 years after the discovery of 
ALK rearrangement in lung cancer, the first-in-class ALK inhibitor (ALKi), 
crizotinib, was approved for metastatic ALK-rearranged NSCLC by the US Food and 
Drug Administration. Subsequently, next-generation ALKis, such as alectinib and 
ceritinib, have been developed, and some of them have been applied in the 
clinical setting. Furthermore, various resistance mechanisms against ALKis have 
been gradually elucidated, and treatment strategies according to such resistance 
have been proposed. In addition, novel ALKis exhibit good antitumor efficacy for 
brain metastases. Thus, we now know much about ALK-rearranged NSCLC; however, is 
it enough? Several concerns, such as the optimal sequence of ALKis, significance 
of antiangiogenic therapy, immune checkpoint therapy, and cytotoxic chemotherapy 
in ALK-rearranged NSCLC, should be clearly addressed, which would lead to the 
establishment of optimal treatment strategies and a more prolonged survival in 
patients with ALK rearrangement. Thus, we should w'ALK' into the next stage.