Patients with cancer are at an increased risk of bacterial infections, which can significantly impact prognosis. Most cases of sepsis and respiratory failure require empiric antibiotic therapy; therefore, awareness of the most frequent pathogens in the oncologic intensive care unit (ICU) and the best antimicrobial treatment strategies are essential for critical care clinicians. In recent years, the epidemiology of bacterial infections in cancer patients has changed with an increasing number of multidrug-resistant Gram-negative bacteria causing infection. Still, the infectious syndrome, type of malignancy, mucositis, antimicrobial prophylaxis, use of invasive devices, and the local epidemiology determine the pathogens causing disease. Multiple variables must be considered when selecting antibacterials in critically ill patients, including drug–drug interactions, toxicities, pharmacokinetics, and pharmacodynamics. This chapter reviews the epidemiology, diagnosis, treatment, and prevention of bacterial infections in the oncologic ICU, focusing on the most frequent pathogens and syndromes.