Both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are classified as autoimmune diseases, where the body’s own immune response causes it to attack the host tissues, as if the latter were antigens. RA is the most common autoimmune disease that affects joints. The clinical diagnosis of RA is based on the history and examination, integrated with laboratory tests including blood tests on inflammatory markers, serology, and imaging. There are no diagnostic criteria, but there are classification criteria. SLE affects most major organ systems in the body. The diagnosis of SLE relies on the constellation of characteristic symptoms, signs, and laboratory findings in the appropriate clinical context and after excluding other reasonable diagnoses. Epidemiologically, both conditions show a definitive female predilection. The focus of this review article is epidemiology, and the major clinical features with an emphasis on the orofacial manifestations. The relevant clinical points for the dental practitioner area summarized.