Chemical force microscopy (CFM) is a name given to the technique whereby ch
emical specificity is added to atomic force microscopy by deliberate deriva
tisation of an atomic force microscopy (AFM) probe. The most fundamental qu
estion that surrounds the technique is-how much 'chemistry' is added. Put a
nother way, how valid is it to interpret image and adhesion contrast in ter
ms of differences in surface chemistry? In this paper three aspects of this
problem are described. In the first, the role of the substrate is discusse
d. Secondly, a series of experiments concerned with the interactions of pi
electron systems is described. These show that it is not possible to interp
ret CFM solely in terms of electronic, or intermolecular interactions. The
third section reviews CFM experiments with chiral surfaces. It is shown tha
t chiral discrimination is not only possible but that the results are in ac
cordance with parallel experiments using high performance liquid chromatogr
aphy (HPLC). Somewhat surprisingly, CFM experiments are more sensitive to c
hirality than HPLC.