Many molecular imaging techniques rely on tracer methods to visualize specific physiological processes in cells, animals, and humans. A new family of "smart" delivery systems for biomolecules has opened new opportunities for the molecular imaging field. One class of polymeric carriers reversibly become membrane destabilizing in response to sharp pH changes and were designed for delivering proteins and nucleic acids to intracellular compartments. These carriers could enable the use of imaging agents and intracellular reporters whose site of action made them previously inaccessible. A second class of stimuli-responsive polymer-biomolecule conjugates can be reversibly formed into particles of closely defined sizes. The ability to control when and where the protein or DNA species is in the free versus particle form may allow imaging applications that exploit their differential size and diffusion properties.