At least 20 clinically relevant factors affect percutaneous absorption of drugs and chemicals: relevant physico-chemical properties, vehicle/formulation, drug exposure conditions (dose, duration, surface area, exposure frequency), skin appendages (hair follicles, glands) as sub-anatomical pathways, skin application sites (regional variation in penetration), population variability (premature, infants, and aged), skin surface conditions (hydration, temperature, pH), skin health and integrity (trauma, skin diseases), substantivity and binding to different skin components, systemic distribution and systemic toxicity, stratum corneum exfoliation, washing-off and washing-in, rubbing/massaging, transfer to others (human to human and hard surface to human), volatility, metabolic biotransformation/cutaneous metabolism, photochemical transformation and photosensitivity, excretion pharmacokinetics, lateral spread, and chemical method of determining percutaneous absorption.