Abstract Non-opioid analgesics encompass the non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol (acetaminophen). The NSAIDs include acetylsalicylic acid (aspirin), dipyrone (metamizole), and numerous other drugs in diverse classes. The NSAIDs have potent anti-inflammatory, analgesic, and antipyretic activities, and are among the most widely used drugs worldwide. In palliative medicine, they represent the first step of the World Health Organization’s analgesic ladder used for mild pain and they are an important supplement to opioids and adjuvant drugs at higher steps of the ladder. The disadvantages of non-opioid analgesics include a ceiling effect for pain relief and the risk of side effects. NSAIDs are associated with an increased risk of adverse gastrointestinal, renal, and cardiovascular effects and hepatotoxicity can result from overdosing with paracetamol. Dipyrone treatment may involve the risk of agranulocytosis. This chapter describes the clinical pharmacology of NSAIDs, their classification, molecular mechanisms of action, and adverse effects.