Fibrosis, the deadly pathological manifestation of an abnormal tissue remodeling in any organ due to excessive collagen deposition, is associated with a wide variety of organ failure-related human diseases. Chronic stress or repeated injury in a particular organ induces abnormal molecular signals that lead to super-activation of matrix protein producing fibroblasts, excessive matrix proteins accumulation, loss of physiological tissue architecture or elasticity, and ultimately leading to organ failure. There is no effective therapy for fibrosis. Factor acetyltransferase p300 (FATp300), a major epigenetic regulator that acetylates specific lysines in histones and transcription factors, is essential for elevated collagen synthesis and the levels of FATp300 are significantly elevated in different fibrotic tissues. Pharmacological inhibition of FAT activity of p300 is associated with decreased collagen synthesis by fibroblasts in tissues and amelioration of organ fibrosis. Therefore, FAT-free p300 is superior for physiological tissue repair and must be exploited as a viable therapeutic target against multi-organ fibrosis. J. Cell. Biochem. 115: 1486–1489, 2014. © 2014 Wiley Periodicals, Inc.