Macrophages are undoubtedly one of the most widely studied cells of the immune system, among other reasons, because they are involved in a wide variety of biological processes. Deregulation of their activity is observed in a number of different disorders, including autoimmune diseases. At the same time, mammalian target of rapamycin (mTOR) is attracting increasing research attention because the pathways dependent on this kinase are activated by a variety of signals, including cytokines and proinflammatory mediators, mediate essential processes for cell survival and metabolism, and can be regulated epigenetically via microRNAs. Therefore, our narrative review aimed to summarize and discuss recent advances in the knowledge of the activation of mTOR signaling in macrophages, with a special focus on autoimmune disorders and the possibility of mTOR control by microRNAs. The summarized research observations allowed us to conclude that the effects of activity and/or inhibition of individual mTOR complexes in macrophages are largely context dependent, and therefore, these broad immunological contexts and other specific conditions should always be taken into account when attempting to modulate these pathways for therapeutic purposes.