Epigenetics, one mechanism by which gene expression can change without any changes to the DNA sequence, was described nearly a century ago. However, the importance of epigenetic processes to neurodevelopment and higher order neurological functions like cognition and behavior is only now being realized. A group of disorders known as the Mendelian disorders of the epigenetic machinery are caused by the altered function of epigenetic machinery proteins, which consequently affects downstream expression of many genes. These disorders almost universally have cognitive dysfunction and behavioral issues as core features. Here, we review what is known about the neurodevelopmental phenotypes of some key examples of these disorders divided into categories based on the underlying function of the affected protein. Understanding these Mendelian disorders of the epigenetic machinery can illuminate the role of epigenetic regulation in typical brain function and can lead to future therapies and better management for a host of neurodevelopmental and neuropsychological disorders.