Heisenberg's matrix formulation of quantum mechanics can be generalized to relativistic systems by evolving in light-front time τ = t + z/c. The spectrum and wavefunctions of bound states, such as hadrons in quantum chromodynamics, can be obtained from matrix diagonalization of the light-front Hamiltonian on a finite dimensional light-front Fock basis defined using periodic boundary conditions in x⁻ and x_⟂. This method, discretized light-cone quantization (DLCQ), preserves the frame-independence of the front form even at finite resolution and particle number. Light-front quantization can also be used in the Hamiltonian form to construct an event generator for high energy physics reactions at the amplitude level. The light-front partition function, summed over exponentially-weighted light-front energies, has simple boost properties, which may be useful for studies in heavy ion collisions. I also review recent work which shows that the structure functions measured in deep inelastic lepton scattering are affected by final-state rescattering, thus modifying their connection to light-front probability distributions. In particular, the shadowing of nuclear structure functions is due to destructive interference effects from leading-twist diffraction of the virtual photon, physics not included in the nuclear light-front wavefunctions.