Imatinib mesylate (Gleevec) is a cellular protein tyrosine kinase inhibitor that inhibits the BCR-ABL tyrosine kinase. This form of targeted therapy has been used for renal cell cancer, chronic myeloid leukemia, and gastrointestinal stromal tumors (GIST). Acute kidney injury, hypophosphatemia, and tumor lysis syndrome have been reported with this agent. We present a 76-year-old woman with a GIST tumor treated with imatinib mesylate. Shortly following the start of treatment, the patient developed acute kidney injury with a serum creatinine of 1.7 mg/dL. A kidney biopsy revealed an acute drug-induced tubular injury. Withholding the agent improved the renal function. Given the extent of her disease, the dose was reduced and she was maintained on treatment. Eight months later there was no radiographic evidence of disease and her renal function remained stable at 1.6 mg/dL. In this paper, we also review the known renal toxicities associated with imatinib. With the increasing use of imatinib and other novel targeted agents for various cancers, it is essential to understand its short- and long-term renal side effects. The acute kidney injury and chronic kidney disease experienced tends to be mild, but the monitoring of serum creatinine is an important part of treatment, especially within the first 3 months. In addition, patients on imatinib need to be monitored for its rarer effects on bone metabolism, such as hypocalcemia and hypophosphatemia.