In normal eyes, retinal detachment (RD) occurs at a rate of approximately 5 per 100,000 people per year and the frequency of proliferative vitreoretinopathy (PVR) remains largely unchanged in primary RD, with the incidence ranging from 5.1 to 11.7%. PVR is the most common cause of failed repair of rhegmatogenous RD, and risk factors for PVR are related to several well-known pre-, intra-, and postoperative clinical situations. Current methods of surgical management of RD and PVR are pneumatic retinopexy, scleral buckling, and pars plana vitrectomy (PPV). Surgical success rates for PVR have improved as techniques and instruments of vitrectomy evolved. However, despite these advances, more than one fourth of initially successful cases results in redetachment due to recurrent vitreoretinal traction. Retinal pigment epithelial cells are the key factor in triggering PVR development. In addition, soluble mediators and the extracellular matrix components play a critical role in cellular events, including proliferation and tissue contraction which occur in PVR. Although PPV remains a critical component of the treatment in RD and PVR, ongoing efforts seek to identify adjuvant therapies that might inhibit PVR development. Recent studies have therefore been directed toward pharmacologic inhibition of cellular proliferation and membrane contraction with drugs such as daunorubicin, 5-fluorouracil, and heparin. More detailed understanding of the pathophysiology underlying PVR may lead to the development of effective prophylactic and/or adjunctive therapies. Further work is necessary to identify optimal adjunctive therapies for the management of RD and PVR.