Topical anesthesia of the skin, nowadays performed for various indications from pruritus over postherpetic neuralgia to minor surgery, has been under investigation for more than 30 years. Due to low water solubility, the active base form of most of the local anesthetics on the market is poorly absorbed through the skin. Hence, the most challenging target was to develop galenic preparations which provide a good skin penetration in order to reach the dermal nerve endings and thereby lead to sufficient local anesthesia. On the other hand good skin penetration also results in a distribution of the drug in the circulation. Since local anesthetic agents are known to have an impact on the heart and central nervous system, unwanted side effects following topical application onto the skin are worth discussing. This article reviews the current topical local anesthetics with particular accent on their pharmacological and toxicological data.