This chapter introduces an advanced content-based image retrieval (CBIR) system, MMIR, where Markov model mediator (MMM) and multiple instance learning (MIL) techniques are integrated seamlessly and act coherently as a hierarchical learning engine to boost both the retrieval accuracy and efficiency. It is well-understood that the major bottleneck of CBIR systems is the large semantic gap between the low-level image features and the high-level semantic concepts. In addition, the perception subjectivity problem also challenges a CBIR system. To address these issues and challenges, the proposed MMIR system utilizes the MMM mechanism to direct the focus on the image level analysis together with the MIL technique (with the neural network technique as its core) to real-time capture and learn the objectlevel semantic concepts with some help of the user feedbacks. In addition, from a long-term learning perspective, the user feedback logs are explored by MMM to speed up the learning process and to increase the retrieval accuracy for a query. The comparative studies on a large set of real-world images demonstrate the promising performance of our proposed MMIR system.