Accumulation of collagen is the major pathologic feature in a variety of fibrotic processes, including dermal fibrosis in progressive systemic sclerosis, morphea, familial cutaneous collagenoma, connective tissue nevi of the collagen type and in keloids. Recent advances in the biochemistry of collagen have allowed us to define specific levels of collagen biosynthesis and degradation at which a pharmacologic intervention can lead to reduced collagen deposition. In this review, we are discussing the mechanisms of action by some of the therapeutic agents currently in use. We further present some new developments involving amino acids and their analogues which could potentially provide us with novel means to reduce the excessive accumulation of collagen in dermal fibrotic processes.