The 21st International Workshop on Principles of Diagnosis (DX'10) will be held in conjunction with the Annual Conference of the PHM Society, PHM 2010, in Portland, Oregon on October 13-16, 2010. The DX Workshop series, initiated in 1989, is rooted in the Artificial Intelligence (AI) community. Papers presented at the workshop cover a variety of theories, principles, and computational techniques for diagnosis, monitoring, testing, reconfiguration, fault adaptive control, and repair of complex systems.