A handheld endoscope has a disposable, single-use portion that includes a distal tip, cannula, housings, and a proximal port that is connected to a substantially straight working channel. The cannula is rotatable about the main longitudinal axis of the cannula. The endoscope also includes a re-usable portion that has a handle and display module. The single-use and re-usable portions mate and un-mate with each other via physical side-mounting arrangement as well as separate electrical connectors. The handle can house imaging system electronics that support manual and auto imaging modes which can be selected via touch screen control on the display module. The re-useable portion is sealed with various o-rings and/or gaskets and can be highly fluid resistant to facilitate disinfecting and/or sterilization.