Gastrointestinal stromal tumors (GISTs) are a rare type of neoplasm arising within the gastrointestinal tract. Current treatment guidelines employ target-based therapy and adjuvant treatment with imatinib mesylate. We report a case of imatinib-induced renal injury in a 48-year-old male undergoing adjuvant chemotherapy after surgical resection of a rectal GIST. Upon initiation of imatinib therapy, the patient’s serum creatinine steadily rose and met criteria for kidney injury after twenty months of therapy. Drug discontinuation led to a normalization of renal function, but upon reinitiating therapy the serum creatinine sharply increased again. The patient’s recurrent acute renal injury led to indefinite drug discontinuation. Imatinib toxicities have been well studied; however, there are no reports to date noting its renal effects in the GIST patient population. This case report highlights imatinib as therapy for GISTs, describes an event of imatinib-induced renal injury, and reviews current treatment modalities.