SummaryAlthough descriptions of quality of life and patient reports of mood in sickle cell disease (SCD) have become more common in the literature, less is known about psychiatric illness prevalence, presentation, and treatment, particularly for adults. We provide a narrative review of what is known about common and debilitating psychiatric conditions such as depression, anxiety, and cognitive impairment, specifically for adults with SCD. We discuss the limitations of the current evidence, make provisional recommendations, and identify opportunities for research and improved care.