The microenvironment has emerged as a promising source of novel therapeutic applications in experimental models of brain metastasis. Our limited understanding of the complex brain ecosystem transformed by the presence of cancer cells includes key cell types that either promote or limit local progression of metastatic cells. Identification of the molecular networks regulating the crosstalk between cancer cells and the microenvironment but also within different brain resident and non-resident cell types surrounding the tumor is crucial to decipher the biology of colonization and subsequently to target key nodes with innovative and effective therapies. Research in the Brain Metastasis Group is supported by MINECO grants MINECO-Retos SAF2017-89643-R (M.V.), Bristol-Myers Squibb-Melanoma Research Alliance Young Investigator Award 2017 (498103) (M.V.), Beug Foundation’s Prize for Metastasis Research 2017 (M.V.), Fundación Ramón Areces (CIVP19S8163) (M.V.), Worldwide Cancer Research (19-0177) (M.V.), H2020-FETOPEN (828972) (M.V.), Clinic and Laboratory Integration Program CRI Award 2018 (54545) (M.V.), AECC Coordinated Translational Groups 2017 (GCTRA16015SEOA) (M.V.), LAB AECC 2019 (LABAE19002VALI) (M.V.), AECC Postdoctoral Grant (POSTD19016PRIE) (N.P.), La Caixa INPhINIT Fellowship (100010434) (P.G-G.), MINECO-Severo Ochoa PhD Fellowship (BES-2017-081995) (L.A-E.). M.V. is a Ramón y Cajal Investigator (RYC-2013-13365) and EMBO YIP (4053). No