The past decade has brought about major advances in the medical management of cancer. Despite these advancements, significant toxicities often accompany the potential benefits of chemotherapy. One of the most common toxicities associated with chemotherapy administration is the development of stomatitis. Stomatitis is estimated to occur in 40% of all patients undergoing chemotherapy, and its incidence is two to three times higher in patients with hematologic malignancies and those undergoing bone marrow transplant. Many inconsistencies currently exist in strategies to prevent, assess, and treat stomatitis. Unresolved or undiagnosed stomatitis can lead to major complications such as poor treatment outcomes, increased cost of care, diminished quality of life, and, eventually, mortality. Oncology nurses share responsibility in improving patient outcomes related to stomatitis by remaining knowledgeable, using evidence-based practice, and ensuring follow-up.