We analyzed publications and articles in the PubMed database about the use of trimethoprim and sulfamethoxazole (TMP-SMX) in dermatology. Literature published in the English language, at least in the past two decades, was reviewed. Specific dermatologic indications for TMP-SMX are few but it is often used as the second- or third- line agent. TMP-SMX is used to treat cutaneous nocardiosis and Aeromonas infections. TMP-SMX is a treatment option for cat - scratch disease, granuloma inguinale, melioidosis and Mycobacterium marinum/fortuitum cutaneous infections. TMP-SMX is an alternate choice for treatment of pyodermas and lymphogranuloma venereum. TMP-SMX has been used to treat acne vulgaris in tetracycline and erythromycin - resistant patients. TMP-SMX is still the preferred empiric antibiotic for methicillin - resistant Staphylococcus aureus skin and soft tissue infection in HIV positive population. TMP-SMX is used in dermatology to treat various skin conditions and is one of the most commonly prescribed sulfonamide drugs. TMP-SMX as monotherapy is an effective treatment option in many diseases but due to drug resistance, a combination therapy-usually of two drugs-may be considered.