Guidelines on how to treat cancer patients receiving cytotoxic chemotherapy in the intensive care unit (ICU) are very limited. Recognizing the severity of the patient, their disease may require the need for chemotherapy whether for localized, metastatic, or hematological malignancies. It may be given alone or in combination with other cancer treatments such as radiation, or hormonal therapies. Nevertheless, the toxicities associated with chemotherapy serve as the driving force for managing complications and safe handling in the ICU. Tumor lysis syndrome, nausea and vomiting, pain management, and adverse medication effects requiring antidotes are complications for patients receiving chemotherapy in the ICU. The administration and safe handling of chemotherapy by nursing is emphasized to provide additional safety precautions. A basic understanding of cytotoxic chemotherapy is reviewed for patients requiring therapy in an ICU.