In parallel with the rapidly growing and widespread use of nanomedicine in the clinic, we are also witnessing the development of so-called theranostic agents that combine diagnostic and therapeutic properties. Among them, ultra-small gold nanoclusters (Au NCs) show promising potential due to their optical properties and activatable therapeutic activities under irradiation. Furthermore, due to their hydrodynamic diameter of smaller than 6 nm and unique biophysical properties, they also present intriguing behaviors in biological and physio-pathological environments. In this review, we aim to present the latest research studies published on such nanoparticles in animals. We also propose guidelines to identify the main physico-chemical parameters that govern the behaviour of Au NCs after administration in small animals, notably concerning their renal elimination and their ability to accumulate in tumors. Then, we present recent advances in their use as theranostic agents putting them in parallel with other contrast agents.