Purpose of reviewTo synthesize evidence and recent advances concerning genetic contributors to autoimmune encephalitis (AE) and paraneoplastic neurological syndromes (PNS), relating these to disease processes and clinical management.Recent findingsThe known immunogenetic role of the human leucocyte antigen (HLA) region - critical to immune and infection response - was refined. A multiethnic IgLON5 study revealed DQ associations, surpassing those previously demonstrated with DR , and arguing for T cell involvement. In PNS with anti-Hu antibodies, a DQB1*02:01 ~ DRB1*03:01 haplotype was preferentially linked to a sensory neuropathy phenotype.Outside the HLA, there were genome-wide association studies (GWAS) in the two commonest AEs. The first AE GWAS with discovery and validation cohorts took place in leucine-rich glioma-inactivated 1-antibody encephalitis (LGI1-Ab-E). This identified a risk locus in PTPRD , a protein tyrosine phosphatase with dual immune and brain activity, and a polygenic risk score (PRS). In N -methyl- d -aspartate receptor-antibody encephalitis (NMDAR-Ab-E), a discovery-only cohort implicated the type 1 interferon pathway gene IFIH1.SummaryGenetic status can perform as a biomarker or prioritize targets for drug development. The paucity of familial cases, the allele frequency of risk HLAs in healthy individuals, and the applicability of PRS, support a multihit model combining genetic and environmental risks.