High-grade gliomas (World Health Organization grades III and IV) are the most frequent and fatal brain tumors, with median overall survivals of 24–72 and 14–16 months, respectively. We reviewed the progress in the diagnosis and prognosis of high-grade gliomas published in the second half of 2021. A literature search was performed in PubMed using the general terms “radio* and gliom*” and a time limit from 1 July 2021 to 31 December 2021. Important advances were provided in both imaging and non-imaging diagnoses of these hard-to-treat cancers. Our prognostic capacity also increased during the second half of 2021. This review article demonstrates slow, but steady improvements, both scientifically and technically, which express an increased chance that patients with high-grade gliomas may be correctly diagnosed without invasive procedures. The prognosis of those patients strictly depends on the final results of that complex diagnostic process, with widely varying survival rates.