A modular grenade launcher system includes an upper chassis and lower chassis secured on opposite sides of a barrel of a weapon, such as a firearm. The chassis removably receives any of a plurality of interchangeable modules, including grenade launcher assemblies having different calibers. A separate modular and removable firing mechanism is provided, wherein multiple grenade launcher barrel assemblies can share a common firing mechanism. An accessory rail module is also provided to replace the grenade launcher barrel assembly and firing mechanism.