Store‐mediated Ca²⁺ entry is the main pathway for Ca²⁺ influx in platelets and many other cells. Several hypotheses have considered both direct and indirect coupling mechanisms between the endoplasmic reticulum and the plasma membrane. Here we pay particular attention to new insights into the regulation of store‐mediated Ca²⁺ entry: the role of the cytoskeleton in a secretion‐like coupling model. In this model, Ca²⁺ entry may be mediated by a reversible trafficking and coupling of the endoplasmic reticulum with the plasma membrane, that shows close parallels to the events mediating secretion. As with secretion, the actin cytoskeleton plays an inhibitory role in the activation of Ca²⁺ entry by preventing the approach and coupling of the endoplasmic reticulum with the plasma membrane, making cytoskeletal remodelling a key event in the activation of Ca²⁺ entry. We also review recent advances investigating the regulation of store‐mediated Ca²⁺ entry by small GTPases and phosphoinositides, which might be involved in the store‐mediated Ca²⁺ entry pathway through roles in the remodelling of the cytoskeleton.