Oral fluoropyrimidines increasingly are being developed and studied as a novel treatment for breast, colorectal, and other cancers. Fluoropyrimidines are designed to generate 5-fluorouracil (5-FU) preferentially within tumors. Cardiotoxicity is a rare complication associated with 5-FU and oral fluoropyrimidine treatments. Chest pain is the most common presenting symptom, and, in many cases, the cardiotoxicity is partly or completely reversible. This article reviews fluoropyrimidine-induced cardiotoxicity and presents a case report of a woman who experienced this complication during capecitabine treatment.