In adults, the sickle cell solubility test (SCST) is the most common screening test to determine the presence of hemoglobin S (HbS) within a blood sample. The assay is inexpensive, rapid, highly sensitive and specific. However, the SCST cannot accurately quantify the level of HbS in a test sample and requires confirmatory testing to distinguish between sickle trait and sickle cell disease. Despite these limitations, it remains the standard screening tool for HbS in a variety of settings such as screening in the US military or by the National Collegiate Athletic Association. With an increased awareness of the importance of screening for sickle cell in adults, we herein describe the current sensitivity, specificity, positive predictive value, and negative predictive value of this test. We also review overall clinical utility of this laboratory measure and briefly discuss new point-of-care techniques designed to overcome the SCST’s shortcomings.