Vaso-occlusive crises (VOCs; also known as sickle-cell-related pain crises [SCPCs]), which are the hallmark of sickle cell disease (SCD), can be precipitated by microvascular occlusion, increased inflammation and physical/emotional distress. De-spitethesubstantialburdenofmorbidityandmortalitycaused by VOCs, there is a paucity of approved preventive therapies that target the processes caused by SCD. Current options impose potential risk to the patient and have highly inconsistent therapeutic effects. Crizanlizumab is a first-in-class, recombinant, humanized monoclonal antibody that blocks interactions between P-selectin (a key VOC pathway modulator), and its ligand P-selectin glycoprotein ligand-1. Preclinical research has guided the initial clinical development of crizanlizumab, yielding insights into its pharmacokinetic/ pharmacodynamic profile and immunogenic properties in healthy volunteers. A phase II study demonstrated that crizanlizumab 5.0 mg/kg significantly lowers the rate of SCPCs versus placebo, and identified no unexpected safety findings. Current findings provide hope that crizanlizumab can deliver disease-modifying effects that prevent VOCs.