The three volume set LNAI 5177, LNAI 5178, and LNAI 5179, constitutes the refereed proceedings of the 12th International Conference on Knowledge-Based Intelligent Information and Engineering Systems, KES 2008, held in Zagreb, Croatia, in September 2008. The 316 revised papers presented were carefully reviewed and selected. The papers present a wealth of original research results from the field of intelligent information processing in the broadest sense; topics covered in the second volume are artificial intelligence driven engineering design optimization; biomedical informatics: intelligent information management from nanomedicine to public health; communicative intelligence; computational intelligence for image processing and pattern recognition; computational intelligence in human cancer research; computational intelligence techniques for Web personalization; computational intelligent techniques for bioprocess modelling, monitoring and control; intelligent computing for Grid; intelligent security techniques; intelligent utilization of soft computing techniques; reasoning-based intelligent systems: relevant reasoning for discovery and prediction; spatio-temporal database concept support for organizing virtual earth; advanced knowledge-based systems; chance discovery; innovation-oriented knowledge management platform; knowledge-based creativity support systems; knowledge-based interface systems; knowledge-based multi-criteria decision support; and knowledge-based systems for e-business.