Hypertrophic scarring and keloid formation are clinical problems with effectively limited solutions. Although numerous methods have been devised to combat them, this article focuses on promising pharmacologic strategies that target collagen metabolism. Laboratory investigations of amino-acid analogs, procollagen peptides, D-penicillamine, and pentoxifylline have demonstrated them to be effective inhibitors of collagen synthesis in cultured cells and/or in animal models. Clinical trials of intralesional administration of interferons have shown impressive reductions in the size and collagen production of keloids. Furthermore, interference of extracellular matrix-enhancing cytokines, such as TGF-beta, may be an effective solution to keloids and hypertrophic scars. Additional research of soluble cytokine receptors, autoantibodies to cytokines, cytokine receptor antagonists, and cytokine-binding molecules may lead to the development of better therapeutic agents.