Mathematical modeling offers a way to critically test experimentally derived theories, integrate experimental results across spatial and temporal scales, and generate predictions to drive bench science and influence clinical practice. Although, in general, mathematical modeling approaches have been applied to narcolepsy only recently, developments in modeling normal sleep/wake behavior have laid an excellent foundation for linking the experimental insights about the orexin (also known as hypocretin) system to the observed features of the narcolepsy phenotype. Thus, many recent models have addressed aspects of narcolepsy including fragmentation of sleep and wake behavior, altered cycling between rapid eye movement (REM) and non-REM (NREM) sleep, sleep onset REM periods (SOREMPs), and cataplexy.