The total synthesis of the potent microtuble stabilizing laulimalide is proposed. Laulimalide is a promising new lead in chemotherapy because of its paclitaxel-like mode of action and its significant in vitro potency. The synthesis centers around the application of asymmetric aldol reactions and the use of an asymmetric glycolate-ring-closing metathesis sequence for the enantioselective construction of the key dihydropyran units.