Hb S polymerization in red cells of people with sickle cell disease results in vascular damage. How this vascular damage occurs is multifactorial, involving viscosity, nitric oxide, oxidative stress, ischemia-reperfusion injury, and activation of leukocytes, platelets and coagulation. Pulmonary hypertension is a manifestation of vasculopathic end-stage organ damage with clinical and prognostic importance. The current status of adenosine A2A receptor agonist therapy will be described, as will plans for an antibody trial against invariant natural killer T cells.