Percutaneous penetration/permeation is a useful tool for obtaining qualitative and/or quantitative information on the amount of a drug, a cosmetic substance, or any chemical that may enter a skin compartment or the systemic circulation of the human body for pharmaceutical or cosmetic purposes, or for toxicological studies. In the latter case, the extent entering can then be taken into consideration in order to calculate the margin of safety using the NOAEL (No Observed Adverse Effect Level) of an appropriate repeated dose toxicity study with the respective substance. This paper is a short overview of various aspects of skin penetration/permeation of drugs or cosmetic agents. The literature reports numerous studies on skin structure and skin properties influencing drug/cosmetic agent permeation profiles and kinetic parameters. The extensive research concerning the skin structure for determining the key parameters of the penetration/permeation process is therefore described first. Mathematical models of the skin absorption process for a drug are then discussed. Finally new developments in pharmaceutical and cosmetic fields to enhance drug permeation or to modify the stratum corneum structure are considered.