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Glioblastoma is the most common type of brain cancer arising from the stem or progenitor neuroglial cells. When abnormal mutations occur in these cells causing changes in the expression of the genes or proteins regulating the cellular pathways, the cells keep on proliferating without any signal to stop and it gives rise to intrinsic malignant brain tumors. According to epidemiological studies, the median age of diagnosis is nearly 65 years, although it can occur even before 65 years. Males are 1.7 fold times more affected than females. Generally, young age and a healthy lifestyle has therapy independent positive prognosis of the disease. Generally Glioblastoma arises due to mutation of the IDH1 or IDH2 gene, with IDH wild type glioblastomas accounting for nearly 90% of the disease. Radiotherapy followed by temozolomide chemotherapy is the current standard care, although the best supportive care is placebo. IDH wild type glioblastoma may arise due to MGMT promoter methylation or unmethylation or it can arise due to EGFR or changes in PI3K/AKT/mTOR pathway, MET gene, FGFR3-TACC3 fusion, BRAF mutation, NTRK mutation. It can also occur due to pRB pathway alterations, loss of p53 function or TERT promoter mutation. In case of programmed cell death, immunotherapy can be opted as a method of treatment. Here, in this article, we will discuss the different types of mutations which give rise to Glioblastoma and focus on the molecular targeted therapies related to different pathways and mutations.