Acute cellular rejection (ACR) is a common complication in liver transplantation recipients (LTRs), especially within the first 12 months, and it is associated with increased morbidity and mortality. Although abnormalities in standard liver biochemistries may raise the clinical suspicion for ACR, it lacks specificity, and invasive liver biopsies, which are associated with numerous risks, are required for definitive diagnoses. Biomarker discovery for minimally invasive tools for diagnosis and prognostication of ACR after liver transplantation (LT) has become a rapidly evolving field of research with a recent shift in focus to omics‐based biomarker discovery. Although none are yet ready to replace the standard of care, there are several promising minimally invasive, blood‐derived biomarkers that are under intensive research for the diagnosis of ACR in LTRs. These omics‐based biomarkers, encompassing DNA, RNA, proteins, and metabolites, hold tremendous potential. Some are likely to become integrated into ACR diagnostic algorithms to assist clinical decision making with a high degree of accuracy that is cost‐effective and reduces or even obviates the need for an invasive liver biopsy.