Recent years have witnessed the rapid development of inorganic nanomaterials for medical applications. At present, nanomedicines-nanoparticles (NPs) destined for therapy or diagnosis purposes-can be found in a number of medical applications including therapeutics (either self-therapeutics or drug carriers) and diagnosis agents (e.g., contrast agents for imaging or transducers in biosensors). Pushing the limits of nanotechnology towards enhanced nanomedicines will surely help to reduce side effects of traditional treatments and to achieve earlier diagnosis. As for all medical approaches, the ultimate aim of nanomedicine is improving the well-being of patients. However, mixing nanomaterials with biological components such as fluids, living cells, and tissues does not always result as expected. The interplay between engineered nanomaterials and biological components is influenced by complex interactions which make predicting their biological fate and performance a nontrivial issue. Indeed, the structural integrity and the a priori function of nanomaterials can change dramatically due to unwanted nano-bio interactions. For medical applications in particular, any new nanomaterial has to be exhaustively studied when it comes in close contact with biological fluids and living cells or organisms. The motivation is clear: first, many unwanted effects can be turned on unexpectedly (e.g., leakage of toxic ions, ROS production, and sequestration by the phagocytic system) and second, their purpose as therapeutic or diagnostic agent can be lost as they are transferred to the desired working environment. This chapter aims to highlight key factors that should be taken into account when choosing and characterizing such functional materials for a given application, with a view to minimizing unwanted nano-bio interactions, rather than providing an exhaustive compilation of recent work. We hope that both early-stage and experienced researchers will find it valuable for designing nanoparticles for enhanced bio-performance.