Conventional treatment of brain tumours includes surgical, radiotherapeutic and chemotherapeutic modalities. Nonetheless, the outcome of patients with brain tumours, in particular glioblastoma, remains poor. Immunotherapy with armed or unarmed monoclonal antibodies targeting tumour-specific antigens has emerged in the last two decades as a novel potential adjuvant treatment for all types of neoplasia. Many challenges to its implementation as a safe and viable therapy for brain tumours still need to be addressed; nevertheless, results from ongoing Phase I/II clinical trials are encouraging, as disease stabilisation and patient survival prolongation have been observed. Advances in preclinical and clinical research indicate that treatment of brain tumours with monoclonal antibodies can be increasingly adjusted to the characteristics of the targeted tumour and its environment. This aspect relies on the careful selection of the target antigen and corresponding specific monoclonal antibody, and antibody format (size, class, affinity), conjugation to the appropriate toxin or radioactive isotope (half-life, range), and proper compartmental administration.