Positrons are widely used in molecular imaging through the positron emission tomography (PET) imaging technique. However PET only reconstruct the distribution of the positron emitting radioisotopes, and because the β + isotopes are linked to a vector molecule, the distribution of β + isotopes is correlated to the distribution of a given biological function.Positron-electron annihilation can transit through a meta-stable called positronium, which can exist in two spin states: 1) the single state-parapositronium and 2) the triplet state-orthopositronium. The orthopositronium lifetime (τ oPs ), formation probabilities and decay modes are sensitive to the physical and chemical state of the neighboring medium and could therefore provide information on the tissues themselves during a PET acquisition. However, traditional PET only relies on the detection of the two annihilation photons, therefore the lifetime and annihilation higher-multiplicity annihilations are not accessible to such PET paradigm.This review will present some of the use cases of positronium as a specific signature for event selection in astrophysics and particle physics, and as a probe for the microscopic state of materials and tissues. These usages of positronium highlight the interest for positronium for diagnostic in medical science, the projects for using positronium in upcoming PET tomographs are then presented.