Autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and systemic sclerosis (scleroderma) preferentially affect women, and are characterized by systemic inflammation leading to target organ dysfunction. The public health burden of autoimmune diseases, which collectively represent a leading cause of morbidity and mortality among women throughout adulthood, is substantial. While some features of these diseases have been observed to improve over the menopausal transition, such as disease flare rate in SLE and skin softening and thinning in scleroderma, others, such as swollen and tender joints and radiographically confirmed damage in RA may worsen. The general trends, however, are not consistent or conclusive for all disease-related manifestations. Of great importance is the recognition that comorbid diseases, including osteoporosis and accelerated cardiovascular disease, contribute excess morbidity and mortality that becomes increasingly apparent as women with autoimmune diseases undergo the menopausal transition.