Magnetic resonance imaging is one of the most efficient diagnostic modalities in clinical radiology and biomedical research. To enhance image contrast, paramagnetic complexes, mainly Gd3+ chelates, are used. In recent years, molecular imaging has emerged as a new area aiming at noninvasive visualization of expression and function of bioactive molecules at the cellular level. This chapter is devoted to the description of supramolecular approaches in the development of highly efficient and smart contrast agents. We demonstrate via representative examples (micellar systems, liposomes, protein-bound chelates, etc.) how supramolecular approaches are applied to increase the efficacy of Gd3+-based contrast agents. We also include an introduction to chemical exchange saturation transfer (CEST) agents and show how supramolecular systems, such as liposomes, can be beneficial to decrease the sensitivity limit of CEST detection. Supramolecular assemblies offer an important advantage regarding the metabolic fate. While covalent polymers are excreted slowly from the body, supramolecular systems facilitate the body elimination via the excretion pathway of the small constituents. Finally, we discuss molecular imaging probes that provide an MRI response mainly through the modulation of supramolecular interactions to various biochemical variables, such as pH, temperature, metal ions, and enzymes.