This chapter begins with one aspect of the chemical ecology of the marine environment, namely the defensive role of polypeptides and surfactants in fish skin secretions. It deals with the phenomenon of defensive-toxic fish skin secretions from ecological and pharmacological points of view. The chapter provides an overview of the current knowledge on the production, delivery and action of toxic fish skin secretions. It also deals with the fish skin secretions that are subdivided into three categories, namely, antibacterial substances, venom glands and ichthyocrinotoxins. In the skin, Tetrodotoxin is found in special secretory glands and is secreted into the surrounding seawater when the fish is agitated. Pahutoxin, a typical cationic detergent, can represent the non-peptide detergents of skin secretions. To summarise, from the point of view of the chemical ecology of the defensive fish skin secretions, sharks provide the perfect classical model of a natural enemy against which such secretions are used.