A multi-axis surgical stapling and cutting instrument. In various embodiments, the instrument includes a tool assembly that operably supports a cable powered knife assembly and further has an anvil that is actuated by axial movement of a closure ring. The instrument may further include a disposable reload unit that may be attached to the reusable portion of the instrument without the use of tools. Various embodiments may also employ an active articulation control system for actively articulating the tool assembly.