Blood cells are subjected to various mechanical forces; including pressure, flow, shear force, gravity, and forces acting against them with varying stiffness (eg. blood vessel wall). Scientists have discovered that these forces have profound effects on cellular growth, differentiation, secretion of cytokines, cell death, and migration. These processes are called mechanotransduction, a conversion of mechanical forces to biochemical signals. In this article the author reviews biophysical forces that affect biological functions of blood cells and their responses in normal physiology and pathophysiology. Although input (forces) and output (cellular responses) have been well studied by utilizing recently developed various force-generating devices, the molecular mechanism of mechanotransudction is still a mystery. This is because reconstructing molecular interaction in the presence of mechanical forces in vitro is highly challenging and until now the molecular dynamics involved in structural changes caused by these forces are largely unknown. Nevertheless, the author has reviewed a few examples of potential structural effects on the molecular mechanism of mechanotransduction.