Described herein are various method of using a direct drive system to perform procedures at a distance. One exemplary method include tying a knot or suturing at a distance with a first and second end effector. The direct drive system can enable sufficient end effector dexterity, including the ability to control various degrees of freedom of end effector movement, and allow a user to perform complicated task at a distance. In one aspect the direct drive system includes flexible tools that permit access to surgical site via a natural orifice.