Medical decompressive therapy (MDT) with corticosteroids and mannitol is often used in patients with primary or metastatic brain tumours. This review highlights the lack of sound evidence regarding the indications and dosage schedule of steroids, prolonged use of which may cause debilitating complications. The available evidence supports the short-term use of MDT for raised intracranial pressure or progressive neurological deficits, but in the absence of these symptoms, MDT is not recommended for stable focal deficits, abnormal higher mental functions, seizures, or as prophylaxis during cranial irradiation. A practical stepladder guideline (based on symptom severity) is proposed with a starting daily dexamethasone dose of 6 mg for non-severe headache and or vomiting; 12 mg for progressive focal neurological deficit with or without non-severe headache or vomiting; and 24 mg dexamethasone with mannitol for severe headache, vomiting, or altered consciousness. Depending on the clinical response, dose can be increased to the next step(s) or tapered every 48 h (more slowly in patients who are dependent on steroids). A scheme for the assessment of efficacy and toxicity prevention is also proposed. The proposed guidelines may be used as a template for further clinical research.