Penicillins belong to the class of ß-lactam antibiotics and have proven to be of value for various dermatologic indications. Both natural and synthetic penicillins delineate applications in the treatment of a number of cutaneous and venereal infections. Besides, these drugs are tolerated well in most cases. Nevertheless, in some patients, side effects are encountered, which can be mild or serious enough to discontinue treatment. This chapter highlights various aspects of the penicillin group of drugs, including the mechanism of action, pharmacokinetics, clinical uses and adverse effects.