The efficacy of azithromycin as sole antimicrobial treatment for infection with Neisseria gonorrhoeae is reviewed. Aggregate cure rates for urethral and endocervical infection were 520/539 (96.5%; 95% CI 94.3% to 97.6%) for a 1 g dose from nine studies and 392/396 (99%; 95% CI 97.5% to 99.6%) for a 2 g dose from two studies. Azithromycin cured 46/47 (97.9%) cases of oropharyngeal infection and 34/35 (97.1%) cases of rectal infection evaluated within the clinical trials. Reports of in vitro resistance to azithromycin reveal a wide geographical spread of clinical isolates, with raised minimal inhibitory concentration to azithromycin and the emergence of high-level resistance in 2001. Concerns about resistance preclude azithromycin from general recommendation as sole antimicrobial therapy for gonorrhoea. However, azithromycin may have a valuable role in specific clinical situations and in combination with extended spectrum cephalosporins in the treatment of gonorrhoea.