Children and adults with sickle cell anemia (SCA) have a higher risk of strokes compared to age- and race-matched peers. Velocity in the middle cerebral or distal internal carotid artery as measured by transcranial Doppler ultrasound is a recognized method to identify children but not adults with SCA at high-risk for first stroke. For both children and adults with SCA that have had a stroke, no methods clearly identify individuals at highest risk of recurrent strokes or an initial silent stroke, the most common neurological injury. Methods to assess cerebral hemodynamics in SCA have been utilized for decades but often required radiotracers making them not feasible for screening and longitudinal follow-up. MRI approaches that do not require exogenous contrast have been introduced and are appealing in both clinical and research scenarios. Improved neuroimaging strategies hold promise for identifying individuals with SCA at increased risk of initial and recurrent infarcts, justifying more aggressive risk-based therapy. We review the epidemiology of stroke in SCA, the impact of strokes, stroke mechanisms, and potential imaging strategies including regional and global oxygen extraction fraction, cerebral blood flow, and vessel wall imaging to identify individuals at high-risk of stroke.