Cardiac arrest (CA) is the primary cause of death in industrialized countries. Successful resuscitation rate is estimated of about 40%, but a good neurological outcome remains difficult to achieve. The majority of resuscitated victims suffers of a pathophysiological entity termed as "post resuscitation disease". Today's efforts are mainly pointed to the chain of survival, often devoting less attention to post-resuscitation care. Resuscitated patients are often victims of nihilistic therapeutic approach, with clinicians failing to promptly institute strategies that mitigate the ischemia-reperfusion injury to vital organs. Only after 72 hours prognostication can be realistically attempted. Neurological evaluation relies on a combination of clinical, instrumental and laboratoristic parameters, since no one alone holds a specificity of 100%. Biochemical markers, such as neuron specific enolase and S-100b, may contribute to predict prognosis after CA. To the contrary, when used individually the necessary precision remains poorly characterized. Biochemical studies suffer from substantial methodological differences hampering attempts to summarize their findings. We review the information available on biochemical markers of brain damage for neurological prognostication after CA.