Glioma is the most common brain tumor, accounting for about 45% of all intracranial tumors. In the past 30 years, the incidence of primary malignant brain intracranial tumors has been increasing year by year, especially in the middle-aged and elderly population. Gliomas are classified into four grades: Grade 1 is benign glioma. Grade II is low-grade malignant glioma. Grade 3 and 4 are highly malignant gliomas. While grade I gliomas are rare, grade IV gliomas account for 50% of all gliomas, so most gliomas are said to be malignant. All grade IV gliomas will recur after surgery. Many people have difficulty in understanding the problem of glioma recurrence, thinking that the doctor opened the tumor off and the doctor said it was clean, how could it still recur? In fact, the degree of complete glioma removal is relative. Generally speaking, if the surgeon removes the tumor visible under the surgical microscope, it is considered clean and is called clinical cure, not biological cure. Due to the infiltrative growth of glioma, the actual extent of the tumor is much larger than what can be seen under the surgical microscope, and the seemingly normal brain tissue in the distant lobes is actually infiltrated with tumor cells. However, even this cannot prevent the recurrence of malignant glioma because the brain tissue has important functions and does not allow arbitrary resection, which may lead to paralysis and coma. For this type of growth of glioma, the surgeon’s ability is limited, so he or she has to resort to radiotherapy and chemotherapy. It has been proven that radiotherapy and chemotherapy do significantly delay the recurrence of malignant gliomas, but glioma recurrence is still inevitable. Compared with the original tumor, recurrent glioma is very different: first, the malignancy of recurrent glioma usually increases, and the original grade 2 becomes grade 3, and the original grade 3 becomes grade 4, which is called tumor evolution; second, the growth rate is faster; third, the blood supply becomes more abundant; fourth, the recurrent tumor may become resistant to the original sensitive chemotherapy drugs. As a result of these important changes, decisions about treatment options for recurrent gliomas are complex. The breakdown is as follows: Reoperation problem: In recurrent glioma, reoperation to remove the tumor and reduce the tumor volume and brain edema may improve the patient’s neurological status, prolong survival, and improve the quality of life. Generally speaking, patients are younger, in better general condition, and can basically take care of themselves; the pathology report of the first surgery is grade II or III glioma; the recurrent tumor is located in superficial non-functional area; the interval between initial and recurrence is relatively long; such patients are more suitable for re-operation. On the contrary, if the patient is old, in poor general condition, already delirious, the original tumor is highly malignant, and the patient recurs soon after surgery, the re-operation will not be of much value. If the recurring glioma is very large in scope, deep in location and invades important functional brain structures, re-operation should be done with great caution. Radiotherapy problem: If no radiotherapy has been done after the initial surgery, routine divided X-ray external irradiation radiotherapy is recommended after recurrence, and postoperative radiotherapy can prolong survival if the surgery is more thorough again. If regular radiotherapy has been done after the initial surgery, recurrent glioma may not be sensitive to ordinary radiotherapy, and gamma knife treatment can be considered, but gamma knife is not effective for very large lesions. Chemotherapy issues: For patients with high-grade glioma who have not received temozolomide chemotherapy in their first treatment, the standard temozolomide chemotherapy regimen (Stupp regimen) is still recommended after recurrence. Temozolomide dose-intensity regimens, and temozolomide in combination with platinum drugs, may be recommended for the treatment of recurrent high-grade gliomas. In patients with recurrent glioma who have had regular temozolomide chemotherapy after initial surgery, the irinotecan in combination with bevacizumab regimen is recommended first and also the methylbenzhydrazine-lomustine-vincristine regimen can be applied. Special mention should be made of bevacizumab, as recurrent gliomas are often rich in blood supply, and bevacizumab is a monoclonal antibody to vascular endothelial growth factor that directly targets neovascularization, which is currently a hot topic of interest in the industry. Since many glioma patients have epilepsy, special attention should be paid in epilepsy medication, as some antiepileptic drugs can reduce the concentration of chemotherapy drugs. Detection of gene mutation helps treatment decision: the essence of malignant tumor is gene mutation, and the essence of tumor evolution is additional gene mutation. Detection of genetic mutations can help scientific decision making by knowing in advance whether a certain radiotherapy measure is effective or not. Gene mutation testing is now in clinical use and is highly recommended by official guidelines. It is important to pay attention to gene mutation characteristics in treatment decisions for recurrent glioma. Novel therapeutic techniques: According to folklore, the treatment of recurrent malignant glioma can be a “dead horse”, and some new therapies that are not widely accepted today can sometimes be used for recurrent glioma. Some of the newer therapies that are not widely accepted today can sometimes be used for recurrent glioma, such as interstitial radiotherapy, interstitial chemotherapy, thermotherapy, immunotherapy, small molecule inhibitors, and intracerebral injections of targeted immunotoxins. For patients who are financially well off, they can also consider participating in clinical trials of new drugs in foreign countries (mainly in the US, Europe and Japan) and treating them with drugs for free, but they have to try to leave the country and enter their treatment centers. Since the national people always look at clinical trials with colored glasses, thinking that clinical trials are to use human body as rats, so there are basically no clinical trials of the latest anti-tumor drugs in China. To sum up, how should recurrent glioma be treated? The answer is personalized treatment – according to the patient’s general condition, the grade and treatment of the original tumor, the site, size, nature of the recurrent tumor, and the type of genetic mutation, to make a comprehensive analysis, scientific decision and integrated treatment for the best efficacy.