In the current management of critically ill patients, variables such as blood pressure, urine output or central venous pressure guide resuscitative efforts. Unfortunately, global tissue hypoxia may persist leading to multiple organ failure and death. To address tissue well-being, indices such as central venous oxygen saturation (ScvO2) and Lactatemia are widely used and are strongly linked to outcome. Implementing these indices in haemodynamic optimization protocols have been shown to reduce morbidity and mortality in numerous studies especially in septic shock. Nevertheless, choosing one index over the other remains controversial. Herein, we review the physiology and rationale for ScvO2 and lactate monitoring. Clinical uses, evidence-based outcome implications and limitations are also examined to aid the clinician in daily practice.