This chapter describes the most advanced to-date QED methods intended to calculate the QED effects in ions, atoms, and molecules with nuclear charge number Z≥ 10. It starts with a brief summary of the conventional QED formalism including the quantization procedure, the perturbation theory, and the renormalization at the one-loop level. Then, the perturbative approach for calculations of energies and transition amplitudes in atomic systems is formulated using the two-time Green’s functions. It is shown how this method can be used to derive an effective Hamiltonion which to the lowest order yields the widely used Dirac-Coulomb-Breit Hamiltonian. The relativistic theory for the nuclear recoil effect is also presented. The current status of the calculations of the QED effects in ions, atoms, and molecules is reviewed. Special attention is paid to the model QED operator approach.