Macrophages are key cellular elements of atherosclerotic plaque pathogenesis and are a significant risk factor for plaque rupture. Current diagnostic techniques for the detection of plaque macrophages are often limited by insufficient sensitivity and selectivity and have not reached broad clinical practice until now. Supramolecular nanometer-sized structures such as conjugates, nanoparticles, micelles, or vesicles built from novel polymers promise to be useful in cell-specific delivery and may be of particular value for the detection and treatment of vulnerable plaque macrophages. Key properties of polymer-based nanostructures are high stability, improved biocompatibility, long circulation half-lives, defined biodegradation, targeting moieties, and triggerable controlled release. This review gives an insight into several promising research projects with polymer-based nanostructures for macrophage detection or treatment that might enter cardiologic practice in the near future.