With recent advances in instrumentation and experimental methodology, noncontact atomic force microscopy is now being frequently used to measure the atomic-scale interactions acting between a sharp probe tip and surfaces of interest as a function of three spatial dimensions, via the method of three-dimensional atomic force microscopy (3D-AFM). In this chapter, we discuss the different data collection and processing approaches taken towards this goal while highlighting the associated advantages and disadvantages in terms of correct interpretation of results. Additionally, common sources of artifacts in 3D-AFM measurements, including thermal drift, piezo nonlinearities, and tip-related issues such as asymmetry and elasticity are considered. Finally, the combination of 3D-AFM with simultaneous scanning tunneling microscopy (STM) is illustrated on surface-oxidized Cu(100). We conclude the chapter by an outlook regarding the future development of the 3D-AFM method.