Azithromycin is used to treat or prevent certain bacterial infections, most often those causing middle ear infections, strep throat, pneumonia, typhoid, and sinusitis. In recent years, it has been used primarily to prevent bacterial infections in infants and those with weaker immune systems. It is also effective against certain sexually transmitted infections, such as nongonococcal urethritis, chlamydia, and cervicitis. Recent studies have indicated it also to be effective against late-onset asthma, but these findings are controversial and not widely accepted.

Azithromycin is used to treat many different infections, including acute otitis media, streptococcal pharyngitis, gastrointestinal infections such as traveler's diarrhea, respiratory tract infections such as pneumonia, cellulitis, babesiosis, Bartonella infection, chancroid cholera, donovanosis, leptospirosis, Lyme disease, malaria, Mycobacterium avium complex disease, Neisseria meningitis, pelvic inflammatory disease, pertussis, scrub typhus, toxoplasmosis, and salmonellosis.^[4] It is used to prevent bacterial endocarditis and some sexually transmitted illnesses post sexual assault.^[4]

It has a similar antimicrobial spectrum as erythromycin, but is more effective against certain Gram-negative bacteria, in particular, Haemophilus influenzae.^{[citation needed]} Azithromycin resistance has been described^[5] and is endemic in many areas. Long-term use in treating Staphylococcus aureus infections with azithromycin may increase bacterial resistance to this and other macrolide antibiotics.^[6]

Azithromycin has been shown to be effective against malaria when used in combination with artesunate or quinine; the optimal dose for this is not yet known.^[7]