The importance of fish skin is realized when one considers that it is the interface between the external and internal environment of the animal. Forming the body’s first line of defense, it comes into direct contact with all waterborne toxic chemicals, parasites, and disease organisms. Skin is one of the largest organs in a fish, making up approximately 10 percent of the body weight, and offers a complex surface that is responsible for maintaining the integrity and constancy of the milieu interieur. Morphologic and functional differences can be great as there are 20 000 species of fish occupying a multitude of habitats in both fresh and saltwater. Many variations in skin composition have evolved to fulfill specific needs of each species, such as sensory organs within the skin, special epidermal and dermal structures and cell types, along with the unique biochemical machinery of the various cell types. Regardless of these many subtle and not so subtle differences, there are basically two major skin layers, the epidermis and dermis with an underlying hypodermis or subcutis recognized in most species. In contrast to the dry, hard, and rather impermeable keratinized skin of mammals, fish skin is continually hydrated, unkeratinized and covered completely by a layer of slimy mucus. Because of the unkeratinized, hydrated nature of fish skin, it can be quite sensitive to waterborne chemicals and physical stressors.