The salicylates are the most commonly used analgesic, antipyretic, and anti-inflammatory drugs. They are available in hundreds of preparations, many of which are over-the-counter medications. The easy access to large quantities of the drug and the widespread perception that the drug is harmless have contributed to salicylate intoxication becoming a serious and common problem, particularly among the pediatric and geriatric populations. Salicylate is still the major drug for the treatment of rheumatic diseases. The use of salicylate in high doses for the management of these patients requires close monitoring of serum salicylate levels because of the large interindividual variation in dose-serum level relationships and the narrowness of the therapeutic range. Thus, both for the management of patients intoxicated with salicylate and patients who are on high-dose salicylate therapy, the measurement of serum salicylate levels is an important clinical laboratory service. Recent research on the inhibitory effect of aspirin on platelet aggregation has led to the prophylactic use of aspirin in low doses as an antithrombotic drug. This new therapeutic use of aspirin can be aided by monitoring low serum levels of salicylate and perhaps aspirin itself. This article reviews the current state of the knowledge of the pharmacokinetics and clinical toxicology of salicylate, the clinical usefulness of salicylate measurement by the clinical laboratory, and recent development in the analytical technology for salicylate analysis.