Sepsis guidelines and mandates encourage increasingly aggressive time-to-antibiotic targets for broad-spectrum antimicrobials for suspected sepsis and septic shock. This has caused considerable controversy due to weaknesses in the underlying evidence and fear that overly strict antibiotic deadlines may harm patients by perpetuating or escalating overtreatment. Indeed, a third or more of patients currently treated for sepsis and septic shock have noninfectious or nonbacterial conditions. These patients risk all the potential harms of antibiotics without their possible benefits. Updated Surviving Sepsis Campaign guidelines now emphasize the importance of tailoring antibiotics to each patient's likelihood of infection, risk for drug-resistant pathogens, and severity-of-illness.