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The fundamental principles underlying the study of dermatotoxicology were developed by Arnold Lehman and John Draize over a half century ago and remain applicable today. This discipline has proven indispensable for addressing the problems associated with skin exposure to chemicals. The 55th anniversary of Lehman's landmark publication on safety factors presents the opportunity to reflect upon the historical beginnings of dermatotoxicology and the role of regulatory policies on the development of this field over the years. The complexity and sheer volume of information that has been collected makes it difficult to comprehensively cover all aspects of this vast discipline. This overview will touch upon the general concepts of ADME, the various forms of contact dermatitis, and transdermal drug delivery systems. The traditional tests performed in animals and humans to identify allergic or irritant potential of chemicals, in addition to alternative methods such as QSAR modeling will be discussed. The subspecialties of infant and occupational dermatotoxicology, as well as dermatotoxicology of aged and ethnic skin, and skin of the vulva and vagina will also be noted.