Early diagnosis and treatment of septic arthritis improves the potential for a favourable outcome. Optimal treatment includes the prompt and judicious use of effective antimicrobial agents coupled with prompt drainage of the affected joint. Adequate drainage may be accomplished by means of repeated closed large-bore needle aspiration, arthroscopy, or an open surgical procedure. The purpose of this article is to describe optimal antimicrobial therapy based upon available pharmacokinetic data. The host-dependent vulnerability to specific pathogens, local antibacterial susceptibility patterns and knowledge of antibacterial activity at the site of infection must all be taken into account when planning appropriate treatment. This article does not address arthritis secondary to human and animal bites, diabetic foot infections, mycobacteria, fungi, Lyme spirochaete, or other nonbacterial causes of septic arthritis.