Sickle cell trait was once considered to benign hereditary condition, besides the association of renal medullary carcinoma, affecting red blood cells. The inherited disorder creates several health issues under various conditions, such as dehydration, hypoxia, or extreme physical exertion. Healthcare professionals and patients with the disorder should understand the importance of vascular complications in sickle cell traits. This article emphasizes the pathophysiology, epidemiology, and molecular basis of the sickle cell trait, which involves virtually every organ system and involves vascular endothelial dysfunction, cerebral vasculopathy, renal complications, cardiopulmonary manifestations, and splenic issues. Techniques of prevention and management strategies for quality-of-life improvement in the case of sickle cell trait are presented.