A crucial challenge in cell biology is to understand how cell surface-associated molecules are organized, and how they interact with their environment. Clarification of these issues is central to our understanding of the functions of cell surfaces (e.g. cell adhesion), and of their implication in biomedicine (e.g. pathogen interactions). The past years have witnessed rapid progress in our use of atomic force microscopy (AFM) to map the distribution of single polysaccharides and proteins on live cells, and to measure their molecular interactions. These nanoscale analyses complement traditional glycomic and proteomic approaches for the functional analysis of surface-associated molecules, and may help in the search for novel drugs. (C) 2009 Elsevier Ltd. All rights reserved.