Tetracycline and its derivatives are frequently used in the treatment of acne, soft tissue bacterial infections, Lyme disease (borreliosis), chlamydial-infections, and respiratory tract infections. Several pharmacologic and microbiological properties of these antibiotics make them particularly suitable for such uses. First-generation tetracyclines have long been in use; however, the second-generation tetracyclines minocycline, doxycycline hyclate, and doxycycline monohydrate have also become widely prescribed, and can offer advantages to the dermatologist over tetracycline. This paper reviews the important pharmacologic and microbiological characteristics of these three commonly used second-generation tetracyclines, and their clinical applications in dermatology.