Purpose of review To review the benefits, risks and specific considerations surrounding antibacterial prophylaxis (ABP) in adults with neutropenia, focusing primarily on high-risk patients with hematologic malignancies (HM) and/or hematopoietic cell transplantation (HCT). Recent findings There has been an overall reduction in benefit of fluoroquinolone prophylaxis (FQP) observed in recent studies, with a lack of overall mortality benefit and less efficacy in reducing Gram-negative bloodstream infections (BSI) rates, which may be explained by increasing rates of fluoroquinolone resistance (both on center-level and patient-level) and improved early sepsis management. In the context of FQP, epidemiology of BSIs has changed with greater Gram-positive BSIs and resistant Gram-negative BSIs. Summary ABP, most frequently FQP, has been introduced since the 1980s with the aim of reducing rates of infection and mortality. While older meta-analyses support its efficacy in reducing episodes of febrile neutropenia (FN), BSI and most importantly mortality, more recent data report lack of benefit on mortality, and negative impacts such as rising antimicrobial resistance, and in the broader literature, safety concerns for FQP. The role of ABP in neutropenia has been increasingly questioned and should be considered at a center-by-center and an individual-patient level.