Research into the effects of nanomaterial surface chemistry and scaffold design in biology has led not only to key advances in the ever-growing field of nanomedicine, but also the discovery of novel tools to answer important biological questions. The exploration of fine tuning nanoparticle chemistry to achieve biological functionality has been extensively investigated for over 4 decades, however, the study of a nanoparticle's geometric design elements, such as size and shape, and their mechanistic influences in biology, remains in its infancy. Though some studies have shown that varying nanoparticle size and shape can have a strong effect on various biological processes such as cell uptake, endocytic pathways, cytokine production, or viral inhibition, the relationship between nanoparticle geometry and biological function remains a fairly under-explored topic for a lot of processes. Moreover, often little has been done to elucidate the specific mechanistic differences caused by shape variation at the molecular level, such as binding affinities or binding modes, which are essential for identifying how nanomedicines work and, perhaps more importantly, for guiding the design of more effective therapeutics.