Several studies have aimed to address the natural inability of humankind to detect deception and accurately discriminate lying from truth in the legal context. To date, it has been well established that telling a lie is a complex mental activity. During deception, many functions of higher cognition are involved: the decision to lie, withholding the truth, fabricating the lie, monitoring whether the receiver believes the lie, and, if necessary, adjusting the fabricated story and maintaining a consistent lie. In the previous 15 years, increasing interest in the neuroscience of deception has resulted in new possibilities to investigate and interfere with the ability to lie directly from the brain. Cognitive psychology, as well as neuroimaging and neurostimulation studies, are increasing the possibility that neuroscience will be useful for lie detection. This paper discusses the scientific validity of the literature on neuroimaging and neurostimulation regarding lie detection to understand whether scientific findings in this field have a role in the forensic setting. We considered how lie detection technology may contribute to addressing the detection of deception in the courtroom and discussed the conditions and limits in which these techniques reliably distinguish whether an individual is lying.