The use of topical remedies in the treatment of disease is as old as medicine itself and the skin being accessible and visible; it is easily amenable to topical therapy. The initial part of this chapter gives the basic principles and terminologies of topical therapy in a nutshell. The later part of the chapter provides noteworthy points on the most commonly used systemic drugs in dermatology pertaining to the pharmacology, dosage, indications, mechanism of action, adverse effects and drug interactions.