Systemic lupus erythematosus (SLE) is a life-threatening multisystem inflammatory condition that may affect almost any part of the eye. We provide an update for the practicing ophthalmologist comprising a systematic review of the recent literature presented in the context of current knowledge of the pathogenesis, diagnosis, and treatment of this condition. We review recent advances in the understanding of the influence of genetic and environmental factors on the development of SLE. Recent changes in the diagnostic criteria for SLE are considered. We assess the potential for novel molecular biomarkers to find a clinical application in disease diagnosis and stratification and in the development of therapeutic agents. We discuss limited forms of SLE and their differentiation from other collagen vascular disorders and review recent evidence underlying the use of established and novel therapeutics in this condition, including specific implications regarding monitoring for ocular toxicity associated with antimalarials.