An increasing number of studies demonstrate the clinical impact of preformed and de novo anti-human leucocyte antigen alloantibody (HLA-Ab) in solid organ transplantation (Tx). The screening of HLA-Ab in candidates and transplant recipients has evolved over time, with continuous improvement in the sensitivity and specificity of assays for HLA-Ab detection. Furthermore, histologic markers of complement activation pathways are currently implemented in the diagnosis of antibody-mediated rejection (AMR). Therapeutic strategies, including depletion of HLA-Ab and B cells, have allowed Tx across antibody barriers, or have rescued patients with AMR. The purpose of the present review is to summarize the state-of-the-art of HLA-Ab detection, clinical significance and therapeutic strategies in pediatric solid organ Tx.