Patients in palliative care take 0-20 drugs, with a mean 5-7. These include drugs used for symptom control, the treatment of concomitant diseases, and in some cases anticancer agents. Drugs used most commonly include: opioids (ap. 80-85% patients), protone pomp inhibitors, glucocorticosteroids (GCs), laxatives, antiemetics (50%), nonsteroidal anti-inflammatory drugs (NSAIDs), benzodiazepines (20 - > 60%), paracetamol (a few to c. 50%), cardiovascular agents and diuretics (30-40%). Neuroleptics (mainly haloperidol) or low molecular weight heparin (LMWH) are administered to 10-20% of patients. In about 20% an antibiotic need to be introduced periodically. Some of them such as ciprofloxacin and clarithromycin are CYP3A4 inhibitors, similarly to antifungal azoles, including fluconazole (used up to > 10%). Multiple of the drugs, particularly opioids, anxiolytics, hypnotics, NSAIDs, GCs and LMWH may cause serious side effects and dangerous drug-drug interactions. The article presents the review of updated literature, with therapeutic implications, that may help physicians to order the most effective and safe management.