The main goal of the present lectures is to outline the key particle interactions and energy loss mechanisms in the Galactic medium that high-energy particles are subject to. These interactions are an important ingredient entering the cosmic ray propagation equation, contributing to shape cosmic ray spectra. They also source the so-called secondary species, like gamma rays, neutrinos, “fragile” nuclei not synthesised in stars, and antiparticles, all routinely used as diagnostic tools in a multi-messenger context. These lectures are complementary to Denise Boncioli’s ones, focusing instead on processes happening at ultra-high energies in the extragalactic environment. They include propædeutic material to Felix Aharonian’s and, to some extent, Stefano Gabici’s and Carmelo Evoli’s lectures.