Diarrhea is common in people with cancer due to a variety of factors, including systemic chemotherapy and newer anticancer therapies, as well as radiation to the pelvis. It is a frequent passage of loose stools with urgency, or more frequent loose stools than is normal for the individual. The gut microbiome is thought to play a key role in the development of diarrhea, including after both radiation therapy and chemotherapy. Patient-related factors for chemotherapy-induced diarrhea (CID) include female sex, colorectal cancer, lactose intolerance, older age, and poor performance status. Treatment-related factors include a range of medications. Patient education should include foods and medications to avoid. Probiotics may reduce CID in patients with cancer; however, the evidence on their efficacy and safety is limited. Treatment-induced diarrhea is a serious side effect of chemotherapy and radiation to the pelvis. Diarrhea has a negative impact on quality of life and may necessitate cessation of treatment.