Molecular imaging plays an important role in the era of personalized medicine, especially with recent advances in magnetic resonance (MR) probes. While the first generation of these probes focused on maximizing contrast enhancement, a second generation of probes has been developed to improve the accumulation within specific tissues or pathologies, and the newest generation of agents is also designed to report on changes in physiological status and has been termed "smart" agents. This represents a paradigm switch from the previously commercialized gadolinium and iron oxide probes to probes with new capabilities, and leads to new challenges as scanner hardware needs to be adapted for detecting these probes. In this chapter, we highlight the unique features for all five different categories of MR probes, including the emerging chemical exchange saturation transfer, 19F, and hyperpolarized probes, and describe the key physical properties and features motivating their design. As part of this comparison, the strengths and weaknesses of each category are discussed.