The aim of this mini-review is to draw attention to the risk aspects associated with antibiotic treatment in critically ill patients. These include antibiotic underdosing in the early phase of sepsis if treatment is governed by pharmacopoeia and unnecessarily long exposure to antibiotics if treatment is guided by traditional recommendations for the length of antibiotic administration. The need for discussing the loading dose of antibiotics and routine monitoring of serum antibiotic concentrations during treatment is stated. Antibiotic-induced mitochondrial dysfunction and oxidative stress are also discussed. Indeed, both of these mechanisms, otherwise effective in inhibiting the growth of tumor cells, may play an important role in the prolonged course of multiorgan failure if antibiotic treatment is too long.