Targeted therapies have been widely used in the treatment of non-small cell lung cancer to improve patient prognosis, especially for EGFR-sensitive mutations with targeted drugs such as gefitinib, erlotinib and afatinib. In 2007, EML4-ALK fusion protein was identified in patients with non-small cell lung cancer. rearrangement of ALK gene leads to signaling that triggers the change of tumor properties. As a new category of non-small cell lung cancer genotyping, so far, two drugs targeting ALK have been approved by FDA for the treatment of non-small cell lung cancer with ALK rearrangement, namely Crizotinib and Ceritinib, and the first one has also been approved for marketing in China. ALK inhibitors have different effects on their targets and are tolerated differently. Crizotinib is an oral tyrosine kinase inhibitor targeting ALK, MET and ROS1. It has an objective remission rate of up to 61% and a progression-free survival of 9.7 months. As second-line therapy for patients with ALK-positive non-small cell lung cancer, Crizotinib and chemotherapy are similarly effective. However, almost all patients experienced tolerance and progression due to gene mutations or activation of the bypass pathway. Second-generation ALK inhibitors have emerged, and a number of second-generation ALK inhibitors are able to overcome Crizotinib tolerance, including Ceritinib and Alectinib, a selective small-molecule ALK tyrosine kinase inhibitor for patients who are resistant or intolerant to Crizotinib. Alectinib is a highly selective ALK inhibitor with an objective remission rate of up to 94% in ALK-rearranged non-small cell lung cancer not previously treated with an ALK inhibitor. It is worth noting that after the application of second-generation ALK inhibitors, attention should be paid to the observation and treatment of possible drug toxicities.