On August 3, 2004, at 2:15 a.m. EST, the MESSENGER mission to Mercury began with liftoff of the Delta II 7925H launch vehicle and 1,107-kg spacecraft including seven instruments. MESSENGER is the seventh in the series of NASA Discovery missions, the third to be built and operated by The Johns Hopkins University Applied Physics Laboratory (JHU/APL) following the Near Earth Asteroid Rendezvous (NEAR) Shoemaker and Comet Nucleus Tour (CONTOUR) missions. The MESSENGER team at JHU/APL is using efficient operations approaches developed in support of the low-cost NEAR and CONTOUR operations while incorporating improved approaches for reducing total mission risk. This paper provides an overview of the designs and operational practices implemented to conduct the MESSENGER mission safely and effectively. These practices include proven approaches used on past JHU/APL operations and new improvements implemented to reduce risk, including adherence to time-proven standards of conduct in the planning and implementation of the mission. This paper also discusses the unique challenges of operating in orbit around Mercury, the closest planet to the Sun, and what specific measures are being taken to address those challenges.