Modification of nano/micro-particle physical parameters (e.g. size, shape, surface charge) has proven to be an effective method to enhance their delivery abilities. Recently, advances in particle synthesis have facilitated investigations into the role that particle elasticity plays in modulating drug delivery processes. This review will highlight: (i) methods to tune particle elasticity, (ii) the role particle elasticity plays in cellular internalization, (iii) the role of particle elasticity in modulating circulation times, (iv) the effect of particle elasticity on altering biodistribution and tissue targeting, and (v) the application of computational methods to explain the differences in cellular internalization of particles of different elasticities. Overall, literature reports suggest a complex relationship between particle elasticity and drug delivery processes. Despite this complex relationship, it is clear from numerous in vitro and in vivo studies that particle elasticity is an important parameter that can be leveraged to improve blood circulation, tissue targeting, and specific interactions with cells.