The purpose of this paper is to discuss both normal perivascular spaces (PVSs) and pathological giant perivascular spaces (GPVSs). The anatomy and physiology of normal PVSs, including important immunological and lymphatic roles, are described. Special attention is given to the Magnetic Resonance Imaging (MRI) findings of both normal and GPVSs. Furthermore, the clinical features and pathogenesis of GPVSs are explored, with special emphasis on the pathological implications of these lesions, and their relevance. It is important that symptomatic GPVSs not be mistaken for more devastating disease processes. When the lesions in question occur in a characteristic location along the path of a penetrating vessel, are isointense with cerebrospinal fluid on all MRI sequences, do not enhance with contrast material, are not calcified, and have normal adjacent brain parenchyma, their appearance is pathognomonic of GPVSs. The clinician should realize that an extensive differential diagnosis is superfluous and that biopsy is unnecessary in these patients. Instead, the clinical focus should be aimed at neurosurgical intervention, as dictated by the symptoms of mass effect.