Reimunde Figueira, Pedro MarcosPensado López, AlbaCarreira Crende, MartínLombao Iglesias, VanesaSánchez Piñón, LauraTorrecilla Parra, MartaRamírez, Cristina M.Anfray, ClémentTorres Andón, Fernando2021-03-122021-03-122021Cancers 2021, 13(5), 1087; https://doi.org/10.3390/cancers13051087http://hdl.handle.net/10347/24730Glioblastoma (GBM) is the most common of all brain malignant tumors; it displays a median survival of 14.6 months with current complete standard treatment. High heterogeneity, aggressive and invasive behavior, the impossibility of completing tumor resection, limitations for drug administration and therapeutic resistance to current treatments are the main problems presented by this pathology. In recent years, our knowledge of GBM physiopathology has advanced significantly, generating relevant information on the cellular heterogeneity of GBM tumors, including cancer and immune cells such as macrophages/microglia, genetic, epigenetic and metabolic alterations, comprising changes in miRNA expression. In this scenario, the zebrafish has arisen as a promising animal model to progress further due to its unique characteristics, such as transparency, ease of genetic manipulation, ethical and economic advantages and also conservation of the major brain regions and blood–brain–barrier (BBB) which are similar to a human structure. A few papers described in this review, using genetic and xenotransplantation zebrafish models have been used to study GBM as well as to test the anti-tumoral efficacy of new drugs, their ability to interact with target cells, modulate the tumor microenvironment, cross the BBB and/or their toxicity. Prospective studies following these lines of research may lead to a better diagnosis, prognosis and treatment of patients with GBMeng© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/GlioblastomaCancerTumor microenvironmentGlioma-associated microglia/macrophagesGeneticsMetabolismmiRNAZebrafishDrug discoveryjournal article10.3390/cancers130510872072-6694open access