The antibiotic therapy in septic syndrome is most often empiric. Decisions and antibiotic choices should result from a careful analysis of past history and setting (hospital-acquired infections vs community acquired infections), risk factors specific to the host, and characteristics of the suspected infections focus: direct examination of body fluid specimens should be obtained rapidly to guide the empiric choice. The choice of antibiotics should conform to usual guidelines, with the aim of a rapid bactericidal effect in blood, while attempting to avoid risks of toxicity. Changes in pharmacokinetics of drugs are usual in this context, and frequent dosing is necessary. While effective antibiotic therapy is a recognized prognostic parameter, antibiotics are only one part of therapy, besides supportive therapy of failing organs, and effective drainage or surgery of the infected focus, when feasible.