The chemistry, mode of action, antimicrobial activity, pharmacokinetics, and therapeutic efficacy of doxycycline are reviewed. Doxycycline displays excellent activity against gram-positive and gram-negative aerobic and anaerobic pathogens. The oral absorption of doxycycline is rapid and virtually complete and is not significantly decreased by food. Moreover, serum concentrations of doxycycline following oral and intravenous (i.v.) administration are comparable. Because of the prolonged half-life of doxycycline, once daily administration is possible. Tissue penetration of doxycycline is excellent. Levels within the therapeutic range have been found in most organs and tissues, including kidney, lung, gallbladder, prostate, intestinal tract, myocardium, sinus secretions, tonsil, aqueous humor, and female reproductive tissue. Doxycycline does not accumulate in patients with renal insufficiency and is not removed from the blood to any great extent during hemodialysis. Extensive clinical investigation has shown doxycycline to be highly effective in infections of the respiratory tract, including atypical pneumonias; skin and soft tissue; genitourinary infection including gonorrhea, syphilis, nonspecific urethritis, and prostatitis; intraabdominal infection due to trauma, sepsis, or surgery; and cholera. Evidence also suggests that doxycycline will prove effective in the treatment of Legionnaires' disease. In addition, placebo-controlled clinical trials suggest doxycycline is effective in the prevention of traveler's diarrhea.