Platelets are specialized adhesive cells that play a key role in normal and pathological hemostasis through their ability to rapidly adhere to subendothelial matrix proteins (platelet adhesion) and to other activated platelets (platelet aggregation). NO plays a crucial role in preventing platelet adhesion and aggregation. In platelets, cGMP synthesis is catalyzed by sGC, whereas PDE2, PDE3 and PDE5 are responsible for cGMP degradation. Stimulation of cGK by cGMP leads to phosphorylation of multiple target substrates. These substrates inhibit elevation of intracellular calcium, integrin activation, cytoskeletal reorganization, and platelet granule secretion, events normally associated with platelet activation. The NO/cGMP pathway also plays a significant role in many other blood cell types in addition to platelets. In leukocytes, depending on the specific cell type, cGMP signaling regulates gene expression, differentiation, migration, cytokine production, and apoptosis.