Rare copy-number variants (CNVs) associated with neurodevelopmental disorders (NDDs), i.e., ND-CNVs, provide an insight into the neurobiology of NDDs and, potentially, a link between biology and clinical outcomes. However, ND-CNVs are characterised by incomplete penetrance resulting in heterogeneous carrier phenotypes, ranging from non-affected to multimorbid psychiatric, neurological, and physical phenotypes. Recent evidence indicates that other variants in the genome, or 'other hits', may partially explain the variable expressivity of ND-CNVs. These may be other rare variants or the aggregated effects of common variants that modify NDD risk. Here we discuss the recent findings, current questions, and future challenges relating to other hits research in the context of ND-CNVs and their potential for improved clinical diagnostics and therapeutics for ND-CNV carriers. Several large-scale studies report additional variants that exacerbate NDD risk in patients carrying pathogenic ND-CNVs. GWAS-derived polygenic risk scores (PRSs) for cognitive and psychiatric phenotypes may influence clinical outcomes by increasing the risk for a given NDD in ND-CNV carriers. Exome sequencing studies of NDD patient cohorts demonstrated the presence of additional, rare, pathogenic single-nucleotide variants (SNVs) in the genomes of ND-CNV carriers. A variety of analytical approaches to integrate genomic variants, including burden testing, variance-component testing, and machine learning, can be applied to interrogate ND-CNV pathogenicity and variable phenotype expressivity in carriers. [ABSTRACT FROM AUTHOR]