Nodding syndrome is a mysterious neurologic illness of unknown etiology, presenting with distinctive clinical features often at early age. Currently, it affects children in restricted geographical areas in South Sudan, Northern Uganda and Southern Tanzania and is associated with high mortality and morbidity, especially in the children with severe disease. In this paper, we will give an outline of what is known about nodding syndrome with respect to epidemiology, clinical presentation, etiology and treatment. In addition, a possible approach to resolving the mystery is presented.