Current and future space missions require agile and reliable spacecraft capable of trailing and keeping the required attitude. Most of the agile spacecraft missions are near-Earth based but some are placed far away from Earth and its influence. One example of such missions is the Athena mission, which requires the spacecraft to perform fast and large-angle attitude slew manoeuvres. Such manoeuvres often imply simultaneous use of multiple actuators such as thrusters and reaction wheels (RWs). A fault in any of these actuators might lead to partial or full damage of sensitive spacecraft instruments. In this research project, a novel model-based Fault Detection and Isolation (FDI) strategy is proposed, which is able to detect and isolate various actuator faults, such as stuck-open/closed thruster, thruster leakage, loss of effectiveness of all thrusters, and change of RW friction torque due to change of Coulomb and/or viscosity factor. Moreover, the proposed FDI strategy is also able to detect and isolate faults affecting the RWs tachometer. The design of the FDI algorithm is based on a multiplicative extended Kalman filter, a generalised likelihood ratio thresholding of the residual signals, and a logic algorithm which unequivocally link the faults to the symptoms. The performance and robustness of the proposed FDI strategy are evaluated using Monte Carlo simulations and carefully defined FDI performance indices. In addition, the influence of faults’ magnitudes, times of fault occurrence, and uncertainties’ magnitudes on the FDI system performance are evaluated. Preliminary results suggest promising performance in terms of detection/isolation times, miss-detection/isolation rates, and false alarm rates. Also, uncertainties on the spacecraft inertia seem to have a negative impact on the FDI performance. In order to fully understand the research project presented here, graduate-level knowledge on rigid body dynamics and kinematics, control theory, and filters applied to estimation might be required. If any of these areas are not known by the reader, it is recommended to read some of the associated literature referenced in the bibliography.