Described herein are various systems and methods for directing endoscopy instruments to varying positions at a target site. In one aspect, at least one instrument channel has multiple exit points at the distal end of the guide tube, and the position of an instrument delivered through the channel may be switched between the different exit points. In another aspect, an instrument channel splits into multiple branches at the distal end of the guide tube, and the position of an instrument at the target site may be changed by selectively directing the instrument into a different channel branch. In yet another aspect, the guide tube, or a portion thereof, may be rotated to reposition an instrument at the target site. The capability of changing the instrument positions during a procedure would enable a physician to examine or treat multiple target sites within an operative field, without necessitating the full retraction of the instruments or the guide tube from the operative field.