Purpose of review Currently, our ability to accurately predict a patient's risk of developing severe gastrointestinal toxicity from their cancer treatment is limited. Risk stratification continues to rely on traditional patient-related and treatment-related factors including age, ethnicity, sex, comorbidities, genetics, agent, dose and schedule. Although informative, these crude measures continue to underestimate toxicity risk, and hence alternative methods of risk prediction must be investigated. Given the increasing focus on the gut microbiome in driving disease, this review will provide an overview of the current literature proposing the gut microbiome as a novel predictive tool for treatment-induced gastrointestinal toxicity. Recent findings Predictive gut microbial phenotypes have been identified for gastrointestinal toxicity induced by radiation and the checkpoint blocker, Ipilimumab. Each study employed slightly different methods of gut microbiome assessment; however, in all cases, separation of toxic versus nontoxic patients was achieved. No studies have investigated chemotherapy-induced gastrointestinal toxicity. Summary The gut microbiome offers an exciting new method of risk stratification for gastrointestinal toxicity. This would enable identification of high-risk patients prior to treatment, enabling tailored treatment regimens based on personalized risk assessment and the proactive provision of supportive care measures. Based on the plasticity of the gut microbiome, methods of risk mitigation may be investigated.