This chapter describes the guidelines for management of sepsis and septic shock. Mortality associated with sepsis remains high and with septic shock it reaches almost 50–60%. Approximately 1400 people die from sepsis each day throughout the world. In the recent definition of sepsis as defined by The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3), sepsis has been defined as change in SOFA score (≥2) or presence of two of the three criteria in qSOFA (Quick SOFA; Altered mental status, RR >22/min, SBP <100 mm Hg) score in the background of infection. This chapter covers the initial resuscitation, screening for sepsis and diagnosis, antimicrobial therapy, source control and infection prevention, fluid therapy, vasoactive medications, blood and blood products, anticoagulants and blood purification, mechanical ventilation, sedation, analgesia, and neuromuscular blockade in sepsis, glucose control, renal replacement therapy and bicarbonate therapy, stress ulcer prophylaxis, nutrition, and deep vein thrombosis prophylaxis.