Abnormalities in the simplest form of learning, habituation, have been reported in a variety of neuropsychiatric disorders as etiologically diverse as Autism Spectrum Disorder, Fragile X syndrome, Schizophrenia, Parkinson’s Disease, Huntington’s Disease, Attention Deficit Hyperactivity Disorder, Tourette’s Syndrome, and Migraine. Here we provide the first comprehensive review of what is known about alterations in this form of non-associative learning in each disorder. Across several disorders, abnormal habituation is predictive of symptom severity, highlighting the clinical significance of habituation and its importance to normal cognitive function. Abnormal habituation is discussed within the greater framework of learning theory and how it may relate to disease phenotype either as a cause, symptom, or therapy. Important considerations for the design and interpretation of habituation experiments are outlined with the hope that these will aid both clinicians and basic researchers investigating how this simple form of learning is altered in disease.