Recent advancements in molecular and synthetic biology, combined with synthetic chemistry and biotechnology, have opened up new opportunities to engineer novel platforms that can monitor complex biological processes with various noninvasive imaging modalities. After decades of using gadolinium- or iron-based metallic sensors for MRI, the recently developed chemical exchange saturation transfer (CEST) contrast mechanism has created an opportunity for rational design, in silico, of nonmetallic biosensors for MRI. These biomolecules are either naturally occurring compounds (amino acids, sugars, nucleosides, native proteins) or can be artificially engineered (synthetic probes or recombinant proteins). They can be administered either as exogenous agents or can be genetically (over)expressed. Moreover, they can be precisely engineered to achieve the desired biochemical properties for fine tuning optimized imaging schemes. The availability of these agents marks the dawn of a new scientific era for molecular and cellular MRI.