Quantification of biologic interactions - from single molecular to macroscopic interfaces - is essential for understanding function in living systems. We will provide a short overview of force probe techniques (AFM, SFA, and optical tweezers) and will then discuss lipid bilayer interactions, and single molecular interaction measurements (under potential control) in detail. These are essential to a vast range of biological functions, such as intracellular transport mechanisms. Surface charging mediated by concentration dependent ion adsorption and desorption on lipid headgroups alters electric double layers as well as van der Waals and steric hydration forces of interacting bilayer and molecules. Two examples will be discussed: First, we characterized the interaction between single hydrophobic molecules quantitatively using atomic force microscopy, and demonstrated that single molecular hydrophobic interaction free energies are dominated by the area of the smallest interacting hydrophobe. The interaction free energy amounts to 3–4 kT per hydrophobic unit. Also, we find that the transition state of the hydrophobic interactions is located at 3 Å with respect to the ground state, based on Bell–Evans theory. Further, we directly measure bilayer interactions during charge modulation in a symmetrically polarized electrochemical three-mirror interferometer surface forces apparatus. We quantify polarization and concentration dependent hydration and electric double layer forces due to cation adsorption/desorption. Results demonstrate that exponential hydration layer interactions effectively describe surface potential dependent surface forces due to cation adsorption at high salt concentrations. Hence, electric double layers of lipid bilayers are exclusively dominated by inner Helmholtz charge regulation under physiological conditions. These results are important for rationalizing bilayer behavior under physiological conditions, where charge and concentration modulation may act as biological triggers for function and signaling. We will finally provide an outlook on combining all force probe techniques with electrochemical potential modulation.