P-selectin belongs to the family of selectin adhesion molecules, and is expressed by platelets and endothelial cells on stimulation. This pattern of expression may indicate an involvement of this molecule in inflammation and coagulation. Data from mice lacking P-selectin expression confirmed this assumption. In addition, a key role of P-selectin in the formation of tumour metastases has been established. Apparently unrelated, clinical experience has pointed towards a detrimental interaction of inflammation and cancer with thromboembolic diseases and vice versa. Therefore, targeting molecules such as P-selectin contributing to coagulation, inflammation and metastasis may offer novel therapeutic strategies to treat chronic inflammatory diseases and metastatic cancer. The authors aim to critically evaluate the contribution of P-selectin in these diseases, and discuss the value of therapeutic inhibition of P-selectin functions in coagulation, inflammation and metastasis.