Rheumatoid arthritis (RA) is a systemic autoimmune and chronic arthropathic disease in which environmental, genetic, and immune factors play a crucial role. The familial history plus the wide range of genetic polymorphisms in affected individuals indicate a hereditary genetic predisposition. Based on the regulatory T cells’ (Treg) function in controlling immunological responses, it has been hypothesized that the genetic polymorphisms in Treg-associated genes might be linked to the loss of immune tolerance in Tregs. Therefore, revealing how missense variations in candidate genes affect disease progression will facilitate the understanding of disease pathophysiology and contribute significantly to the design of superior therapies for RA. In this study, we highlight the genetic polymorphisms that influence Tregs in their generation, function, signaling, and stability, due to the apparent effect of Tregs dysfunction on the RA pathogenesis and other autoimmune diseases. Knowing some general concepts, we now turn our attention specifically to describing the identified polymorphisms in many different ligand-receptor interactions and developmental pathways of Treg cells.