Fluorescence microscopy has become an indispensable tool in cell biology because it allows specific proteins to be visualized. Atomic force microscopy (AFM) is also becoming extensively used in the life sciences, but its development has largely followed an independent path and is used for somewhat different, but often complementary, purposes. Both methods can be applied to hydrated biological samples. The development of combined optical microscopy and AFM instrumentation, as offered by Veeco’s BioScope II, has not only addressed some of the key limitations of both individual techniques, it has now opened the door for researchers to apply this type of integrated instrumentation to study fundamental challenges in cell biology and biophysics.