This chapter gives an overview on antimicrobial therapy including management of septic shock. The proper use antibiotics can produce favorable therapeutic results. All appropriate microbiological samples should be taken before starting antibiotics. Rapid tests, like an immediate Gram stain report, may provide clue to the right antibiotic to be used if empiric therapy is being considered. Choice of antibiotic should depend on likely pathogen, clinical diagnosis, and coexistent conditions. The need for antibiotics should be reassessed daily. For most infections encountered 5–7 days of antimicrobial therapy is usually sufficient. Monotherapy with an effective agent aims to decrease the drug antagonism between two agents and the undesirable side effects of multiple antibiotics. A detailed discussion on management of septic shock has been provided in this chapter.