Methods and apparatus assist in planning routes through hollow, branching organs in patients to optimize subsequent endoscopic procedures. Information is provided about the organ and a follow-on endoscopic procedure associated with the organ. The most appropriate navigable route or routes to a target region of interest (ROI) within the organ are then identified given anatomical, endoscopic-device, or procedure-specific constraints derived from the information provided. The method may include the step of modifying the viewing direction at each site along a route to give physically meaningful navigation directions or to reflect the requirements of a follow-on live endoscopic procedure. An existing route may further be extended, if necessary, to an ROI beyond the organ. The information provided may include anatomical constraints that define locations or organs to avoid anatomical constraints that confine the route within specific geometric locations or a metric for selecting the most appropriate route. For example, the metric may define the closest route to the ROI such that the route satisfies all applicable anatomical, device, and procedural constraints.