The atomic force microscope (AFM) allows biomolecules to be observed and manipulated under native conditions. It operates in buffer solution, produces molecular images with outstanding signal-to-noise ratio, and addresses single molecules. Progress in sample preparation and instrumentation has led to topographs that reveal sub-nanometer details and surface dynamics of biomolecules. Antibodies or oligonucleotides immobilized on cantilevers induce bending upon binding of the cognate biomolecule, allowing sub-picomolar concentrations to be measured. Biomolecules tethered between support and retracting AFM-tip produce force extension curves that reflect the mechanical stability of secondary structure elements. Furthermore, multifunctional tips may activate single molecules to observe them at work. In all cases, the cantilever is critical: its mechanical properties dictate the force-sensitivity and the scanning speed.