Genomic disorders are a group of human genetic diseases caused by genomic rearrangements resulting in copy-number variation (CNV) affecting a dosage-sensitive gene or genes critical for normal development or maintenance. These disorders represent a wide range of clinically distinct entities but include many diseases affecting nervous system function. Herein, we review selected neurodevelopmental, neurodegenerative, and psychiatric disorders either known or suggested to be caused by genomic rearrangement and CNV. Further, we emphasize the cause-and-effect relationship between gene CNV and complex disease traits. We also discuss the prevalence and heritability of CNV, the correlation between CNV and higher-order genome architecture, and the heritability of personality, behavioral, and psychiatric traits. We speculate that CNV could underlie a significant proportion of normal human variation including differences in cognitive, behavioral, and psychological features.