We review the present status of the theory of high energy reactions with semi-exclusive nucleon electro-production from nuclear targets. We demonstrate how the increase of transferred energies in these reactions opens a complete new window in studying the microscopic nuclear structure at small distances. The simplifications in theoretical descriptions associated with the increase of the energies are discussed. The theoretical framework for calculation of high energy nuclear reactions based on the effective Feynman diagram rules is described in details. The result of this approach is the generalized eikonal approximation (GEA), which is reduced to Glauber approximation when nucleon recoil is neglected. The method of GEA is demonstrated in the calculation of high energy electro-disintegration of the deuteron and A = 3 targets. Subsequently we generalize the obtained formulae for A > 3 nuclei. The relation of GEA to the Glauber theory is analyzed. Then based on the GEA framework we discuss some of the phenomena which can be studied in exclusive reactions, these are: nuclear transparency and short-range correlations in nuclei. We illustrate how light-cone dynamics of high-energy scattering emerge naturally in high energy electro-nuclear reactions.