Transcranial Doppler (TCD) is widely accepted as the modality of choice for screening intracranial vessels in children with sickle cell disease. Its advantages are that it is noninvasive (no need for sedation, contrast material, or radiation), portable, easily repeated, and it provides information about the intracranial vessels that is otherwise unavailable. These positive attributes explain why in recent years the applications for TCD have grown beyond sickle cell screening to almost any disease process that involves the major intracranial vessels. The objective of this manuscript is to discuss key points on how to perform and interpret TCD, and discuss imaging features of various pathological processes such as sickle cell, asphyxia, brain trauma, brain death, hydrocephalus, enlarged subarachnoid spaces, vasospasm, vasculitis, venous sinus thrombosis, and vein of Galen malformation.