The delivery of nanoparticles through receptor-mediated cell interactions has nowadays a major attention in the area of drug targeting applications. This specific kind of targeting is mediated by localized receptors impeded into the target site with subsequent drugs internalization. Hence, this type of interaction would diminish side effects and enhance drug delivery efficacy to the target site. Somatostatin receptors (SSTRs) are one type of G protein-coupled receptors, which could be active targeted for various purposes. There are five SSTRs types (SSTR1-5) which are localized at various organs in the body and spread into different tissues. SSTRs could be considered as a promising target to various nanoparticles which is facilitated when nanoparticles are modified through specific ligand or coating to allow better binding. This review discusses the exploration of SSTRs for active targeting of nanoparticles with certain emphasize on their interaction at the cellular level.