Background: Glioblastoma multiforme (GBM) is one of the most aggressive and common primary malignant brain tumors, comprising 16% of all primary brain and central nervous system neoplasms, with a grim prognosis despite maximal treatment. Median age of presentation is 65 years. Patients often present with symptoms of increased intracranial pressure, including headache and focal or progressive neurologic deficits. The recurrence of GBM is inevitable, its management often unclear and case dependent. The purpose of our study was to analyse the role of Intensity Modulated Radiotherapy (IMRF) with concurrent and adjuvant chemotherapy in Glioblastoma. Methods: In our study we retrospectively analysed the treatment outcome of 84 patients of Glioblastoma, treated in our institute Gandhi Medical College, Hamidia Hospital and Jawaharlal Nehru Cancer Hospital, Bhopal between July 2010-December 2014. Patients were divided into 2 groups and proper consents were taken to participate in clinical trial. A group of 42 patients were treated by traditional method of surgery and WB (Whole-brain) RT alone and other group patients were treated with maximal safe surgical resection, followed by concurrent intensity modulated radiotherapy, IMRF (started after 1 month) in 1.8–2 Gy fractions administered 5 days per week with temozolomide (TMZ) at a dose of 75 mg/m2 daily for 6 weeks and then adjuvant chemotherapy was started with TMZ 150 mg/m2 daily for 5 days for the first month. If tolerated, the dose is escalated up to 200 mg/m2 for 5 consecutive days per month for 1 year. Results: With an average follow-up of three years in 84 patients of GBM, group of patients treated with surgical resection and concurrent IMRF with TMZ, after surgery followed by adjuvant TMZ for one year demonstrated superior Progression Free Survival (PFS) of 15 months versus months with surgery and RT alone, as well as superior Overall Survival (OS) of 28 months versus 14 months with other group. The 5 year OS rate was <1% in 1st group and 5-10% in other group. Patients with WB (Whole-brain) RT developed endocrinopathy, neurocognitive toxicity and leukoencephalopathy. IFRT delivers external beam RT to the tumor with a 2–3 cm margin and hence minimises toxicity. Conclusions: This study shows the effectiveness of treating GBM patients with maximal safe surgical resection, followed by concurrent IMRF and TMZ and adjuvant chemotherapy with TMZ for long time. It not only improves PFS but also improves OS. Further understanding of underlying tumor biology is essential in developing more effective strategies. Research in gene therapy, antiangiogenic antagonists, combination chemotherapy and immunotherapies could be a ray of hope in treating GBM. Given the aggressive and resilient nature of GBM, continued efforts to better understand GBM pathophysiology are required to discover novel targets for future therapy. Clinical trial identification: GMC2508IND17 Legal entity responsible for the study: Gandhi Medical College, Bhopal, India Funding: Gandhi Medical College, Bhopal, India Disclosure: All authors have declared no conflicts of interest.