Size and shape are fundamental properties of micro/nanoparticles that are critically important for nanomedicine applications. Extensive studies have revealed the effect of particle size on spherical particles with respect to circulation, extravasation and distribution in vivo. In contrast, the importance of particle shape has only recently begun to emerge. For example, cylindrically-shaped filomicelles (diameter 22-60 nm, length 8-18 μm) have shown persistent blood circulation for up to one week after intravenous injection, much longer than their spherical counterparts. Disc-shaped nanoparticles have demonstrated higher in vivo targeting specificity to endothelial cells expressing intercellular adhesion molecule receptors in mice than spherical particles of similar size. In this Minireview, we will discuss the recent advances in the fabrication of shape-specific nanoparticles and their unique biological and pharmacological properties. Computational models are presented to provide mechanistic understanding of the shape effects on cell targeting under flow conditions. Shape-specific nanoparticles have the potential to significantly improve the performance of nanomedicine in diagnostic imaging and targeted drug delivery applications.