Functionalised nanoparticles for biomedical applications represents an incredibly exciting and rapidly growing field of research. Considering the complexity of the nano–bio interface, an important question is to what extent can theory and simulations be used to study these systems in a realistic, meaningful way. In this review, we will argue for a positive answer to this question. Approaching the issue from a “Soft Matter” perspective, we will consider those properties of functionalised nanoparticles that can be captured within a classical description. We will thus not concentrate on optical and electronic properties, but rather on the way nanoparticles’ interactions with the biological environment can be tuned by functionalising their surface and exploited in different contexts relevant to applications. In particular, we wish to provide a critical overview of theoretical and computational coarse-grained models, developed to describe these interactions and present to the readers some of the latest results in this fascinating area of research.