Drone systems and methods for package pickup and delivery include, in an air traffic control system configured to manage UAV flight in a geographic region, communicating to one or more UAVs over one or more wireless networks; directing a UAV to pick up the package at the pickup location and to deliver the package to a delivery location; and directing the UAV, in transit, to travel along at least one of a road, highway, and street for a predetermined distance and at a predetermined altitude.