PALS is one of the most widely used "nuclear probe" techniques for the tracking of the structural characteristics of materials. The method is based on the matter-energy equivalence principle recognized by Einstein: the electrons and positrons as particle-antiparticle pairs disappear in mutual destruction of particles, they annihilate with high-energy gamma-radiation, thus "particle-energy transition" occurs. The properties of the resulting radiation exactly correspond to the relevant properties of the electron and positron preceding the annihilation. Since electrons occur in all types of materials, the phenomenon of positron annihilation can play in any environment; consequently the method can be used for the analysis of each type of materials (crystalline and amorphous, organic and inorganic, biotic and abiotic). The present paper provides an overview of the theoretical physical background, the practical realization and evaluation of methods, their limitations, and summarizes the pharmaceutical applications published in recent years.