Doxycycline is sometimes effective for trivial infections of the upper respiratory tract or of the (genito-)urinary tract but it does not represent the drug of choice. It is considered the drug of choice for an array of less frequent problems. It is particularly well suited for atypical pneumonia (as long as a legionella infection can be excluded), for disease following Chlamydia trachomatis (non-gonorrhoeal urethritis, acute urethral syndrome, venereal lymphogranuloma, etc.), for brucellosis (in combination with e.g. rifampicine), for rickettsial diseases (spotted fever, Q fever), for cholera and for anthrax. Doxycycline can be applied in stage I of Lyme disease. The efficacy for papulopustular acne is also well documented.

Doxycycline is considered an alternative drug for syphilis when there is e.g. a hypersensitivity to penicillin. It is recommended as a follow-up treatment to a single dose of ceftriaxone for the treatment of possible chlamydia infections in context with gonorrhoea. It is used in combination with other antibiotics for acute inflammatory pelvic disease caused by mixed infections. It can also be used for the prophylaxis of traveler's diarrhea. Doxycycline can also be considered for the prevention or treatment of multiresistant malaria (e.g. in Thailand).

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