Molecular imaging has emerged at the end of the last century as an interdisciplinary method involving imaging and molecular biology aiming at identifying living biological processes at a cellular and molecular level in a noninvasive manner. It has a profound role in determining disease changes and facilitating drug research and development, thus creating new medical modalities to monitor human health. At present, a variety of different molecular imaging techniques have their advantages, disadvantages, and limitations. In order to overcome these shortcomings, researchers combine two or more detection techniques to create a new imaging mode, such as multimodal molecular imaging, to obtain a better result and more information regarding monitoring, diagnosis, and treatment. In this review, we first describe the classic molecular imaging technology and its key advantages, and then, we offer some of the latest multimodal molecular imaging modes. Finally, we summarize the great challenges, the future development, and the great potential in this field.