Peyronie's disease (PD) is a superficial fibrosing disorder that causes penile deformity and can interfere with sexual intercourse and reproduction, as well as diminish quality of life. While the exact mechanism of PD is still being investigated, there is likely a genetic component to the predisposition to penile plaque formation. Ultimately, however, perturbations in normal wound healing and aberrant deposition of extracellular matrix components lead to fibrotic tissue deposition. Fibrosis in PD is regulated by a complex pathway of inflammatory and fibrotic mediators. Currently there are no treatments for PD that address an underlying cause or disease progression. In this review, we provide an overview of the known inflammatory and fibrotic mediators of PD and explore the pathophysiology of other human superficial fibrosing disorders to develop further insights into PD.