Quantum fluctuations in mesoscopic tunnel junctions are studied in the presence of high charging energies. The processes of sequential tunneling, electron cotunneling and resonant tunneling are analyzed within a new nonperturbative resummation technique. The current and the average charge are shown to be related to the spectral density describing the charge excitations of the single electron transistor. An energy-dependent finite lifetime is obtained which leads to the theory of inelastic electron cotunneling and gives important corrections to the classical result for strong tunneling and finite temperatures. An additional energy renormalization leads to a logarithmic temperature dependence of the renormalized system parameters. Several formulas for the line shape of the conductance oscillations are presented which show the possibility to observe experimentally quantum fluctuation effects at realistic temperatures.