The landscape of sickle cell disease (SCD) treatment continues to evolve rapidly, with new disease-modifying therapies in development and potentially curative options on the horizon. Until recently, allogeneic stem cell transplant has been the only proven cure for SCD. Gene therapy is rising to the forefront of the discussion as a potentially curative or highly disease-modifying option for abating the complications of the disease. Understanding the different types of gene therapy in use, the differences in their end points, and their potential risks and benefits will be key to optimizing the long-term use of this therapy.