A method of sequestering skin irritants consisting essentially of the step of topically applying to the human or animal a skin irritant sequestering composition, the composition consisting essentially of a substrate and both a hydrophilic sequestering agent that sequesters skin irritants and a hydrophobic sequestering agent that sequesters skin irritants, and at least one of the group consisting of anti-inflammatory agents, antimicrobials, anti-puretics, skin protectants, α-hydroxy acids, microbial extracts, algal extracts, fractions of microbial extracts, fractions of algal extracts, enzyme inhibitors, antihistamines, antioxidants, analgesics, astringents, natural vitamin analogs, synthetic vitamin analogs, and mixtures thereof, wherein the skin irritant sequestering agent is present in an amount between about 0.01% and about 1.0% by weight of the composition, and the hydrophilic sequestering agent is selected from the group consisting of clays, bentonite, kaolinite, laponite, zeolite, montmorillonite, beidelite, hectorite, saponite, stevensite, calcium carbonate, talc, silica, titanium oxides, hydroxyapatite, alumina, aluminum silicate surfactants, calcium silicate activated carbon, pearl starch, calcium sulfate, antibodies, ion-exchange materials, cyclodextrins, lectins, Lewis acid/base materials, activated charcoal, glass microspheres, diatomaceous earth reactions, refractory metal oxides, and combinations thereof, and the hydrophobic sequestering agent is selected from the group consisting of modified clay, modified silica, modified titanium oxides, modified refractory metal oxides, cyclodextrins, and combinations thereof, and at least one of the sequestering agents can bind irritants selected from a group consisting of cytokines, eicosanoids, enzymes, superantigens, proteases, lipases, glycosidases, bile aids, endotoxins, bacterial by-products, and combinations thereof.