Rathke’s cleft cysts are typically regarded as benign cystic lesions of the sella that may affect the pituitary gland and on occasion the visual apparatus. They are most commonly incidental and rarely of clinical significance. As medical neuroimaging and surgical technologies have rapidly advanced, so too has the discovery, experience, knowledge, and intrigue concerning this relatively rare disease entity. Nevertheless, numerous controversies still exist regarding its natural history, recurrence rate, predictive variables, and optimal surgical management. This chapter aims to review the pathogenesis, symptomatologic manifestations, radiographic, morphologic and histopathological characteristics, treatment strategies and outcomes in the cysts of Rathke’s cleft.