Sickle cell disease (SCD) is an autosomal, recessive, genetic condition of the sickle cell genes. It affects about 100 000 people in the United States where an estimated 1 out of every 365 black children and 1 out of every 13 black children will be born with SCD and sickle cell trait, respectively. Severe and unpredictable pain crisis are the leading cause of emergency department visit for adult patients with SCD and account for 90% of inpatient hospitalizations and 85% of all acute medical care, as well as high usage of medical resources. The care of patients with SCD is complex and requires a multidisciplinary approach. With a few pharmacotherapeutic options to reduce SCD complications and pain episodes, the role of pharmacists in the medication management is unclear. This article aims to outline the potential role of pharmacists in SCD management. The authors searched Medline, PubMed, EMBASE, and Scopus from January 1, 1990 to August 31, 2022, for primary literature that assessed the role of pharmacists in managing patients with SCD. The authors identified relevant studies and summarized the role of pharmacists in SCD management. Access to comprehensive health care is essential to ensure that patients with SCD have decreased hospitalizations and good health-related quality of life. Pharmacists are an integral part of the multidisciplinary health-care team and can help patients with SCD navigate the complexities of health care. Pharmacists are medication experts who are positioned to ensure comprehensive care in the acute and chronic SCD management.