This chapter examines the complex idea of criminal responsibility from a neuropsychological standpoint, exploring the relationship between brain activity and guilt in legal situations. Readers learn how brain disorders, diseases, and injuries can impact a person’s ability to comprehend the nature and repercussions of their actions as well as their capacity to behave in a way that complies with the law through an examination of case law and empirical research. The chapter also looks at how criminal responsibility standards are changing and how neuropsychological evidence affects culpability decisions in court. Case studies highlight the difficulties in deciding cases involving neurological disabilities by illuminating the intricate interactions between neurobiological elements and legal conceptions of intent and moral responsibility. Important lessons include the need for sophisticated knowledge of the variables determining criminal guilt and the consequences for the judicial system, and sentence guidelines when dealing with people who have neurological impairments.