(1) Background: Tacrolimus is an immunosuppressive agent commonly used in the management of solid organ allogeneic transplants in the prevention of rejection. Serious ophthalmic adverse effects with Tacrolimus have been reported in the literature, which includes cortical blindness and optic neuropathy. (2) Methods: We describe a rare case of maculopathy as a possible complication of Tacrolimus therapy. A 56-year-old man receiving Tacrolimus for immunosuppression after liver transplantation developed unilateral visual disturbance with a central scotoma. (3) Results: Ophthalmologic examination revealed unilateral maculopathy; a Tacrolimus macular toxicity was suspected. After drug discontinuation, a complete visual recovery was observed; however, the ultrastructural macular damage was irreversible. (4) Conclusions: Reports regarding maculopathy associated with Tacrolimus are limited. This case report adds to the current literature regarding the possible macular toxicity of this immunosuppressive agent, especially if it exceeds therapeutic serum levels. Further data are needed to confirm this possible association. A careful ophthalmologic examination should be promptly performed in patients manifesting visual disturbance while taking Tacrolimus to prevent irreversible, permanent vision loss due to possible drug toxicity.