Etminan et al 1 performed a population-based, retrospective case-control study evaluating the association between retinal detachment (RD) and oral fluoroquinolone use in a population of patients under ophthalmological care. Substantial evidence implicates these agents with tendinitis and tendon rupture, raising a concern that an increased risk of RD might follow from a shared mechanism of collagen degradation 2 that could affect the vitreous of the eye. Oral fluoroquinolones are commonly prescribed, possibly even overprescribed, 3 such that a public health risk may be posed. However, until now, only anecdotal reports of RD after oral fluoroquinolone use exist. These drugs penetrate rapidly into the vitreous cavity of the eye. 4 Clinicians must now grapple with the findings of Etminan et al of a 4.5-fold elevation in RD risk with oral fluoroquinolone use. How convincing is this information, and should we change our prescribing behaviors based on this report? To illuminate this issue, we discuss herein (1) a physiological background for RD; (2) validity and generalizability of the findings of Etminan et al; (3) a perspective on the amount of purported increased risk of RD; and (4) how physicians might currently approach these findings in clinical practice.Degenerative changes in the vitreous can lead to synchisis (gel liquefaction with fluid cavity formation) and syneresis (collapse of the vitreous body), processes that can lead to dehiscence of the vitreous body from the retinal surface. This sequence of events, termed posterior vitreous detachment at its more advanced stages, usually occurs without untoward effects because there is weak vitreoretinal adhesion. In the presence of firm vitreoretinal adhesion, however, vitreous dehiscence can lead to vitreous traction, retinal tears, and rhegmatogenous RD. 5 It is likely that most of the RDs ascertained in the study were rhegmatogenous, based on the predominance of this mechanism in the general population. These occur mostly in persons older than 50 years, 6 but various genetic collagen disorders affecting the vitreous body, such as Stickler and Marfan syndromes, are associated with RD in both adults and children. It is thus conceivable that a drug in-terfering with collagen integrity may increase risk. Although the molecular mechanism by which fluoroquinolones might affect vitreous humor remains speculative, a study on collagen metabolism in tendon tissue suggests a possible mechanism. Fluoroquinolones upregulate matrix metalloproteinase 2, leading to increased cleavage of