Prostaglandin analogs are powerful ocular hypotensive agents that may also be associated with a breakdown of the blood-retinal barrier and cystoid macular edema. The association is evident in pseudophakic or aphakic patients. This paper presents a case of unilateral latanoprost-associated clinical cystoid macular edema in a bilaterally pseudophakic patient; the only difference between the two eyes was the presence of a capsulotomy in the affected eye. We review the literature concerning prostaglandin analog-associated cystoid macular edema, as well as the evidence for prostaglandin analog-associated breakdown of the blood-retinal barrier. Although some evidence is suggestive of a connection between prostaglandin analogs and cystoid macular edema, many questions concerning the complex physiology of prostanoids remain. Until our understanding of these issues is more advanced, judicious use of prostaglandin analogs in patients at risk for cystoid macular edema would be prudent.