The available research on humor, mirth, or laughter in neurology, nervous disorders, and diseases is sparse and fragmented. This review attempts to collect, collate, and evaluate available evidence afresh in this research paper. Although descriptive, the included literature covers around eighty peer-reviewed published articles written exclusively on the chosen theme. The anatomical, organic, evolutionary, and functional basis is delineated before specific neurological disease conditions are invoked to understand how humor is believed to be generated, appreciated, or can be even used as an adjunct form of therapy to ameliorate these conditions. The opportunities and challenges for humor research in the contemporary scenario for neurology are summarized with a plea for more empirical work in this direction.