Improved management of infectious complications of acute myeloid leukemia (AML) has contributed substantially to the success of care over the past half century. An important approach to reducing infectious complications during the induction period of chemotherapy involves the use of prophylactic antibacterial, antiviral, and antifungal agents targeting likely pathogens.There is not a one-size-fits-all approach to prophylaxis; every patient undergoing induction therapy should be evaluated individually and within the context of local microbiologic epidemiology and host risk factors. Pharmacologic and non-pharmacologic interventions as well as novel diagnostic platforms can help mitigate the risk of life-threatening infection in patients with AML who undergo induction chemotherapy.