The detergent solubilization and reformation of phospholipid vesicles was studied for various detergents. Two distinct mechanisms of vesicle-to-micelle and micelle-to-vesicle transition were observed by turbidimetry and cryo-electron microscopy. The first mechanism involves fast solubilization of phospholipids and occurs via open vesicular intermediates. The reverse process, micelle-to-vesicle transition, mimics the vesicle-to-micelle transition. In the second mechanism the solubilization is a slow process that proceeds via micelles that pinch off from closed vesicles. During vesicle reformation, the micelle-to-vesicle transition, a large number of densely packed multilamellar vesicles are formed. The route used, for solubilization and reformation, by a given detergent-phospholipid combination is critically dependent on the overall packing parameter of the detergent-saturated phospholipid membranes. By a change of the overall packing parameter the solubilization and or reformation mechanism could be changed. All five detergents tested fit within the proposed model. With two detergents the mechanism could be changed by changing the phospholipid composition or the medium conditions.