Methods and devices for approximating tissue are disclosed. The methods and devices utilize a device for applying an implantable tissue fastener and a variety of implantable tissue fasteners. The tissue-fastening device can be delivered endoscopically and can be adapted to function along side or in conjunction with a flexible endoscope. In general, the device can include a flexible shaft having an implantable tissue fastener applier disposed at a distal end thereof and a handle for operating the implantable tissue fastener applier disposed at a proximal end thereof. A variety of self-deploying implantable tissue fasteners can be used with the tissue fastener applier device.