Once severe sepsis or septic shock is recognized, resuscitative measures should be initiated immediately, if not already under way. Efficient delivery of broad-spectrum antimicrobial therapy is a treatment of critical importance. Potential sources of infection, common pathogens, patient risk factors, and local resistance patterns should be considered to determine the ideal drugs for first-line administration. These should almost always include broad bacterial coverage (Gram-positives, Gram-negatives, and anaerobes), may often be directed at resistant Gram-positives such as methicillin-resistant Staphylococcus aureus (MRSA) and/or vancomycin-resistant enterococci (VRE), and may occasionally target virulent Gram-negative bacilli and/or fungi. In patients with severe sepsis, the use of an antipseudomonal penicillin (such as piperacillin/tazobactam), a fourth-generation cephalosporin (such as cefepime), or a carbapenem (such as meropenem) is recommended; alternatively, an antipseudomonal fluoroquinolone (such as ciprofloxacin) in addition to metronidazole is suitable for those with a beta-lactam allergy. The use of vancomycin (for MRSA coverage) or linezolid (for VRE coverage), aminoglycosides (for extended Gramnegative coverage), and fluconazole (for antifungal coverage) is often indicated for patients experiencing septic shock or specific cases of severe sepsis.