The success in identifying the chromosomal rearrangements involving the 
anaplastic lymphoma kinase (ALK) as an oncogenic driver has thoroughly changed 
the treatment of non-small-cell lung cancer. In the past decade, targeted drugs 
have emerged as an efficient personalized strategy for ALK-rearranged 
non-small-cell lung cancer. The accelerated approval of potent ALK inhibitors, 
such as crizotinib and more recently ceritinib (LDK378), based on the well 
designed phase I/II trials has been a landmark success in clinical cancer 
research and contributes a new era of oncogenic targeted therapy characterized 
by elegant clinical trial design. In this review, we aim to present the current 
knowledge on acquired resistance of crizotinib known as a first-in-class ALK 
inhibitor and potential solutions to improve the cost-effectiveness, and to 
review the difference between ceritinib and crizotinib; preclinical data and 
results of the elegant early clinical trial of ceritinib which promoted its 
accelerated approval, pharmacokinetics, safety profile, and tolerability, the 
updated results (eg, efficacy on brain metastases), and robust design of ongoing 
phase II/III trials, and future directions of ceritinib to be a potent 
alternative to crizotinib for ALK-rearranged non-small-cell lung cancer are also 
presented.