Starting with the application of tyrosine kinase inhibitors (TKI) to the treatment of slow granules, the long-term survival rate of patients has been significantly improved. Patients who take the drugs regularly, on time and at the right dosage for a long period of time can have survival rates close to those of healthy people of the same age. In recent years, some experts have suggested that patients with chronic granulocytes treated with TKI drugs may have the opportunity to stop taking the drugs after their disease has stabilized, further enhancing the confidence of patients with chronic granulocytes to adhere to the drugs. There are currently two generations of tyrosine kinase inhibitors available in China: the first generation Imatinib, the second generation Nilotinib and Dasatinib. Is it true that the newer the drug, the better the effect? Many patients are very confused about how to choose between the two generations of drugs. Here we will answer this question. There is no significant difference in the long-term survival rate between the two generations of drugs. In the treatment of slow particles, patients need to check the fusion gene quantification regularly to determine the effect of the drug. In terms of the speed and depth of decrease of fusion gene quantification, the second generation drugs are better than the first generation drugs, proving that the effect of killing tumor cells is stronger and faster. However, in terms of the long-term survival rate of patients after drug administration, second-generation drugs did not surpass the first-generation drugs. Therefore, if only from the perspective of ensuring survival, the first-generation drugs are still a reasonable treatment that can be trusted. However, from the perspective of successful discontinuation, second-generation drugs have a better chance of reaching the “discontinuation threshold” (i.e., molecular remission MR 5.0 or higher) than first-generation drugs because of their faster and stronger suppression of fusion genes, thus allowing more patients to have the opportunity to discontinue their attempts. Two generations of drugs, with slightly different populations Imatinib has been around for a long time and has significant therapeutic efficacy, which makes it different from second-generation drugs in terms of the population it is used in. Because imatinib has been in clinical use for a longer period of time and has lower adverse effects, the strategy for managing adverse effects while taking imatinib is more mature for patients with multiple chronic diseases. Therefore, patients with combined chronic diseases such as hypertension and diabetes should prefer imatinib; patients who are older and do not pursue future drug discontinuation can also choose imatinib. Second-generation drugs have a stronger ability to kill tumors, allowing fusion genes to drop faster and deeper, enabling more patients to enter the “discontinuation threshold”. Therefore, younger patients who wish to have a chance to stop taking the drug in the future may consider taking second-generation drugs. Many people have the mentality of keeping a hand in the game, thinking that they can use first-generation drugs first and then use second-generation drugs after they are resistant to the drugs. Tumor cells are different from other cells, if they are given a chance to breathe, they will grow wildly. Therefore, in the treatment of malignant tumor, we should adopt the treatment method of “heavy hammering” to “beat” the tumor cells at once. At present, there are few cases of direct preference for second-generation drugs, but the therapeutic effect of second-generation drugs on slow-growing tumors is recognized. Most patients still start with first-generation drugs because of the long duration of their use. In this case, once the drug is not effective, the patient should switch to second-generation drugs as soon as possible. If a patient develops resistance to a second-generation drug (which is less likely), the two second-generation drugs can be used interchangeably because they differ in the resistance gene; however, it is necessary to test for the presence of the resistance gene before switching. If both drug generations do not work well, patients should consider hematopoietic stem cell transplantation as soon as possible. In summary, the choice of the two generations of drugs should be based on the patient’s age, underlying disease, the need for therapeutic effect and consideration of adverse effects.