A significant amount of work has been carried out in drug delivery system (DDS) research in recent years using a large variety of techniques. The use of AFM has enabled us to directly observe very small objects without the need of a cumbersome and potentially contaminating sample preparation. Thus, nanoscale DDS can be investigated in a controlled environment without the necessity of staining or drying. Moreover, intermittent contact mode AFM allows the investigation of soft samples with minimal sample alteration; phase imaging allows accessing information beyond the sample’s topography and also differentiating between different materials, and force spectroscopy experiments help us to understand the intrinsic structure of DDS by recording the elastic or adhesion behaviour of particles. Hence, AFM enables us accessing information which is hardly available by other experimental techniques. It has provided invaluable information about physicochemical properties and helped to shed light on the area of nanoscale drug delivery and will, with more and more sophisticated equipment becoming available, continue to add to our understanding of the behaviour of nanoscale DDS in the future.