Nowadays, flight qualified Field Programmable Gate Array (FPGA) contains millions of gates. This technology enables many new applications in mission operations such as in-flight reconfiguration for fault recovery, in-flight reconfiguration for resource planning in different mission phases, multiple science objectives spacecraft, and technology upgrade during long life missions. On the other hand, the new applications will also create many new challenges for mission operations. These challenges include how to reconfigure the hardware of the spacecraft in flight, how to transmit the large reconfiguration file to the spacecraft, and how to verify the reconfiguration is executed correctly. This paper will examine the issues and solutions to these challenges. First, a brief survey of the current FPGA technology and the process to reconfigure these devices will be provided. Second, the avionics architectural support to facilitate the in-flight reconfiguration will be discussed. Third, the mission operation procedures and uplink/downlink process to reconfigure the spacecraft in-orbit will be described. The main concern of these procedures is the safety of the spacecraft during and after the reconfiguration. Finally, a set of commands and telemetry required to execute the in-fight hardware reconfiguration will be proposed.