Medical Informatics and the application of modern signal processing in the assistance of the diagnostic process in medical imaging is one of the more recent and active research areas today. This thesis addresses a variety of issues related to the general problem of medical image analysis, specifically in mammography, and presents a series of algorithms and design approaches for all the intermediate levels of a modern system for computer-aided diagnosis (CAD). The diagnostic problem is analyzed with a systematic approach, first defining the imaging characteristics and features that are relevant to probable pathology in mammo-grams. Next, these features are quantified and fused into new, integrated radio-logical systems that exhibit embedded digital signal processing, in order to improve the final result and minimize the radiological dose for the patient. In a higher level, special algorithms are designed for detecting and encoding these clinically interest-ing imaging features, in order to be used as input to advanced pattern classifiers and machine learning models. Finally, these approaches are extended in multi-classifier models under the scope of Game Theory and optimum collective deci-sion, in order to produce efficient solutions for combining classifiers with minimum computational costs for advanced diagnostic systems. The material covered in this thesis is related to a total of 18 published papers, 6 in scientific journals and 12 in international conferences.