Squalor-dwelling behavior has been characterized as living in conditions so unsanitary that feelings of revulsion are elicited among visitors. This behavior is commonly associated with an insensitivity to distress/disgust and a failure to understand the direness of one's living situation, which leads to social isolation and impairment in quality of life. Etiologically, several associations have been described in the literature, including age-related decline, lower socioeconomic status, and rural dwelling status. Primary neuropsychiatric disorders, such as psychosis, alcoholism, dementia, personality disorders, developmental delays, and learning or physical disabilities are frequently seen in squalor-dwelling individuals. However, none of these disorders seems to be necessary or sufficient to explain the behavior. Neurobiologically, squalor-dwelling behavior has been associated with frontal lobe dysfunction as evidenced by executive dysfunction; however, cognitive impairments also fail to completely explain this behavior. The purpose of this report is to describe a typical case of squalor-dwelling behavior and use it as an example to illustrate the complexity of uncovering the neurobiological basis for this maladaptive personal and public health threat. Neuroimaging findings from our case and a review of the literature point toward decreased activity in the insular cortex and the amygdala as a unifying biological explanation for squalor-dwelling behaviors.