In conventional, Scanning Tunneling Microscopy (STM) the tip—sample separation is assumed to be sufficiently large to allow only weak coupling between the electronic states. In this case the electrodes have been considered to be independent. In some operating modes of STM the tip—sample separation is purposely set small to enhance the tip—sample interaction and hence to modify the electronic and atomic structure irreversibly. Indeed, as the tip approaches the sample surface, the potential barrier is lowered, the charge density is rearranged and the ions in the vicinity of the tip are displaced to attain the minimum of the total energy at the preset tip—sample distance. Modifications of the electronic and atomic structure depending upon the tip—sample separation have led to the identification of different regimes in the operation of STM; ranging from the independent electrodes to the irreversible mechanical contact. This chapter deals with the tip—sample interaction effects. The variation of electronic structure and vacuum barrier, the character of conduction and tip force are investigated as a function of separation. Our analysis suggests that operation of the tunneling and force microscopes under a significant tip—sample interaction will bring about potential applications not only in the investigation of electronic and atomic structure but also in mesoscopic physics.