Atomic force microscopy (AFM) has become an important tool for understanding the nano- to molecular scale mechanisms predominant in multiphase systems. In flotation research, the use of AFM holds promise for unlocking and establishing fundamental mechanisms, ultimately leading to significant advances in process performance. From measuring and characterising surface forces, the structure of molecules at interfaces, and nanoscale features on flotation media, AFM is a powerful tool that has only begun to impact flotation research. Highlights of advances made in the utilisation of AFM for flotation research at the University of Florida are given with an emphasis on interpreting the mechanisms behind calcium activation in phosphate flotation and the impact of nanoscale asperities on collector-born surface hydrophobicity.