Systemic lupus erythematosus (SLE), commonly referred to as lupus, is a widely prevalent chronic autoimmune disease that can affect any organ system in the body. Although the pathogenesis of this disease is rather complex and poorly understood, ultimately there is an overproduction of multiple self-reactive antinuclear antibodies. These autoantibodies are one of the laboratory hallmarks of the diagnosis and disease activity of SLE. Lupus has a myriad of symptoms and imaging manifestations. Serositis, one of the most common manifestations of the disease, usually occurs with pleural or pericardial effusion with or without associated serosal inflammatory changes. The pulmonary manifestations are heterogeneous, with mostly acute (eg, diffuse alveolar hemorrhage, acute lupus pneumonitis) and some chronic (eg, fibrosing interstitial lung disease, shrinking lung syndrome) lung findings. Cardiac and vascular manifestations include myocarditis; coronary artery disease, including accelerated atherosclerosis; myocardial infarction; and spontaneous dissections, along with vasculitis, aneurysms, Libman-Sacks endocarditis, and arterial and venous thromboembolism. Although patient history and risk factor assessment have a vital role in diagnosing lupus, familiarity with the imaging manifestations aids radiologists in optimizing patient care, assessing for complications, and uncovering undiagnosed cases of lupus. This fact emphasizes the importance of recognizing the complex multisystem involvement of lupus seen at imaging. In this article, the authors review the thoracic and cardiovascular imaging manifestations of lupus. © RSNA, 2024.