Six rationales for using combination analgesics are identified, but most combinations are formulated with two rationales in mind: enhancement of analgesia and reduction of adverse effects by combining two analgesics with different mechanisms of action. Acetaminophen and aspirin are the mainstays of oral analgesic combinations. There is substantial evidence that combining an optimal dose of acetaminophen or aspirin with an oral opioid such as codeine, hydrocodone, or oxycodone produces an additive analgesic effect greater than that obtained by doubling the dose of either constituent administered alone. There is also some evidence that the adverse effects produced by such combinations are less than would be produced by an equi-analgesic dose of a single constituent. The physician need not be confined to existing fixed-ratio combinations; he or she may extemporize to the patient's advantage by co-administering acetaminophen, aspirin, or other nonsteroidal anti-inflammatory drugs with available oral opioids and, in select situations, co-administering oral or injectable analgesics with psychoactive drugs.