The use of bicarbonate is rooted in three decades of clinical experience and observational studies. For many years, bicarbonate passed the tried and true test for clinical therapies; however, administration of sodium bicarbonate during cardiac arrest and hypoxic acidosis has become increasingly controversial. The controversy provides an excellent opportunity to evaluate the impact an evidence-based approach might have on a common clinical practice. Is bicarbonate efficacious in the treatment of the severe acidosis that accompanies cardiac arrest during cardiopulmonary resuscitation (CPR)? Are the deleterious effects of bicarbonate clinically relevant? What is the evidence upon which a rational decision may be based? This review evaluates and ranks the evidence supporting the use of sodium bicarbonate in the therapy of acidosis associated with cardiac arrest during CPR.