Introduction: Acute liver failure (ALF) is a condition that can rapidly progress to multiorgan failure. Therefore, different extracorporeal liver support systems have been developed to function as a bridge to transplantation or spontaneous survival. Conversely, the shortage of organs demands a rigorous selection process to determine whom should receive transplantation and several prognostic models have been proposed to identify the patients who would benefit the most from liver transplantation (LT). Objectives: A review of the main selection criteria used for LT in ALF is carried out, focusing mostly on the new proposed prognostic markers, and aiming to identify poor prognosis criteria associated with futility in LT. Extracorporeal liver support systems (ECLS) were also reviewed, including an analysis of their impact on the survival of patients with ALF. Methods: MEDLINE and PubMed databases were searched between 16th October 2021 and 5th December 2021. The inclusion criteria were: adult patients; patients with acute liver injury (ALI) or ALF; observational studies; clinical studies; case series; case-control studies; systematic reviews; meta-analysis. Discussion: King’s College criteria (KCC) have been widely used and despite good specificity, have low sensitivity. Several markers have been used to improve prognostic accuracy, but the results are not sufficiently clear. Patient age, ABO incompatibility, and poor-quality grafting were potential factors that could indicate potential futility in LT. ECLS have a positive influence in clinical and laboratory parameters; however, there is no clear evidence of improvement in survival. Conclusion: ALF is a heterogeneous syndrome, which brings into question of the studies carried out to evaluate prognostic criteria to select patients for LT. It also narrows down the studies performed to evaluate the impact of ECLS on survival.