The pterygopalatine fossa (PPF) is a small, clinically inaccessible, fat-filled space located in the deep face that serves as a major neurovascular crossroad between the oral cavity, nasal cavity, nasopharynx, orbit, masticator space, and the middle cranial fossa. Due to its inherent complex location and connections, it can potentially act as a natural conduit for the spread of inflammatory and neoplastic diseases across the various deep spaces in the head and neck. This review aims to acquaint the reader with the imaging anatomy of the PPF, its important communications, and to identify some major pathological conditions that can involve the PPF, especially in conditions where its involvement can have serious diagnostic and therapeutic implications, such as in perineural tumour spread.