Observations show that there are two components of positron annihilation radiation from the region of the Galactic Center: a variable component resulting from one or just a few compact sources at or near the Galactic Center and a steady, diffuse component resulting from positron annihilation in the galactic disk. We model the diffuse component using the observed longitude distributions of 70–150 MeV gamma rays, CO, and hot plasma revealed by Fe line emission. We review recent results on positron annihilation in the interstellar medium and discuss the implications of the annihilation processes on the fraction of positrons annihilating via positronium and on the shape of the 511 keV annihilation line. We also review the sources of diffuse galactic positrons and discuss the nature of the compact source of annihilation radiation near the Galactic Center.