For many years, sepsis guidelines have focused on early administration of antibiotics. While this practice may benefit some patients, for others it might have detrimental consequences. The increasingly shortened timeframes in which administration of antibiotics is recommended, have forced physicians to sacrifice diagnostic accuracy for speed, encouraging the overuse of antibiotics. The evidence supporting this practice is based on retrospective data, with all the limitations attached, while the only randomized trial on this subject does not show a mortality benefit from early administration of antibiotics in a population of patients with sepsis as often seen in the emergency department (ED). Physicians are challenged to treat patients suspected of having sepsis within a short period of time, while the real challenge should be to identify patients who would not be harmed by withholding treatment with antibiotics until the diagnosis of infection with a bacterial origin is confirmed and the appropriateness of a course of antibiotics can be evaluated more adequately. Therefore, in the general population of patients with sepsis, taking the time to gather additional data to confirm the diagnosis should be encouraged without a specific timeframe, although physicians should be encouraged to perform an adequate work-up as soon as possible. Patients with suspected sepsis and signs of shock should immediately be treated with antibiotics, as there is no margin for error.