Sepsis in patients with cirrhosis is associated with high mortality. An impaired immune response accounts for the increased infection risk observed in these patients. Hemodynamic and systemic changes suggestive of sepsis may be observed in patients with cirrhosis in the absence of infection; therefore, diagnosis and treatment of sepsis may be delayed. The optimal management of the critically ill patient with sepsis and cirrhosis has not been well established and is generally extrapolated from consensus guidelines and expert recommendations made for management of patients without cirrhosis with sepsis. Despite the lack of strong evidence, we propose a contemporary pragmatic approach to sepsis management in patients with cirrhosis, including the choice of fluids, vasopressors, and antibiotics.