All non-opioid analgesics are believed to act via inhibition of cyclo-oxygenase. With respect to their inhibitory potency towards the enzyme, these drugs differ not only from most non-steroidal anti-inflammatory drugs but also among themselves. The differences appear to be of some therapeutic relevance. They explain why many non-steroidal anti-inflammatory drugs are unsuitable for over-the-counter (OTC) use and why the OTC drugs have different profiles of effects and side effects. In addition, the suitability of non-opioid analgesics in everyday practice is widely determined by their pharmacokinetic parameters. These parameters are here compiled for aspirin, paracetamol (acetaminophen), ibuprofen, and metamizol (dipyrone), then compared, and finally evaluated as to their therapeutic implications.