Regorafenib (BAY 73-4506, Stivarga® Bayer HealthCare Pharmaceutical Inc) is an oral multikinase inhibitor with a distinct and wide-ranging profile of tyrosine kinase inhibition, resulting in antiangiogenic and antiproliferative properties in tumors. Single-agent regorafenib administered as a 160-mg daily dose for the first 21 days of a 28-day cycle is approved for use in patients with pretreated metastatic colorectal cancer (mCRC) and gastrointestinal stromal tumor (GIST) progressing on imatinib and sunitinib, following publication of data from the phase III CORRECT and GRID studies respectively. Regorafenib is currently under phase III investigation in patients with hepatocellular carcinoma and is in several phase II studies in patients with gastrointestinal (GI) tumors. This review describes the clinical development of regorafenib in patients with GI cancers, and highlights the key issues important for the modern day clinical pharmacist who forms part of the multidisciplinary team ensuring safe and effective delivery of the drug to the patient. This information is considered of particular importance to the clinical pharmacist for the future development of regorafenib in this treatment setting.