Crizanlizumab and voxelotor were several of the first drugs to receive FDA approval for sickle cell disease (SCD) since the approval of hydroxyurea in 1998. Although initially exciting, additional data regarding efficacy and safety have since emerged for both drugs, first with the removal of crizanlizumab from the European market in August 2023. This was followed by Pfizer's abrupt decision in September 2024 to pull voxelotor from global markets due to higher mortality in those on the drug versus placebo. These drugs highlight the importance and limitations of the FDA accelerated approval process. In addition, the impact of these events, without transparent messaging, potentially threatened the fragile trust that providers have more recently been able to build with the SCD population regarding the medical system and research. While there is a need for new therapies in SCD, we must prioritize both safety and efficacy, and maintain trust in this population.