Human microbiota is composed of approximately 3 × 1013 commensal bacteria and other microorganisms that live on the epithelial barriers of the host, and influence many physiological functions including the maintenance of local intestinal homeostasis and systemic regulation of host metabolism, hematopoiesis, inflammation, immunity, and other functions. Recently, it has been reported that microbiota imbalance (dysbiosis) may play a critical role in the development of multiple diseases, including metabolic, cardiovascular, and neurological alterations. In this context, scientific advances have significantly contributed to our understanding of the complex connection between microbiota and cancer. We are continuously exposed to microbial cells, both resident and transient, as well as their metabolites, including toxic compounds. The main purpose in this work is to review and summarize the current knowledge of the pro- and anti-carcinogenic role of microbiota, and its influence in the efficacy and toxicity of chemotherapy, immunotherapy, and radiotherapy. Indeed, current evidence suggests that microbiota could provide new insights into the basic mechanisms of carcinogenesis. A better understanding of the role of microbiota in cancer may lead to the development of individualized interventions through the modulation of microbiota, to increase the efficacy of antitumoral treatment, or to prevent or ameliorate adverse effects.