Introduction: The survival of SLE patients has improved significantly over the past few decades placing them at increased risk of cardiovascular disease (CVD), malignancies, and osteoporosis, among other comorbidities. The aim of this review was to assess the incidence and prevalence of comorbidities in these patients as well as their prevention and treatment focusing in CVD, malignancies and osteoporosis. Areas covered: We focused on CVD, malignancies and osteoporosis as SLE comorbidities. A literature search (PubMed database) was performed using the words ‘comorbidities’, ‘cardiovascular disease’, ‘osteoporosis’, ‘malignancy’, ‘cancer’ and ‘lupus’ between January 1976 and December 2016. No language restrictions were placed. More than 100 full-length articles were reviewed. Expert commentary: The therapeutic approach in SLE should aim not only at achieving disease remission but also at treating all conditions affecting the patients and, consequently, their outcomes. These patients should be treated as coronary artery disease (CAD) equivalent with rigorous modifiable CV risk factors management in addition to the optimal treatment of their lupus. Furthermore, modifiable osteoporosis traditional risk factors and SLE-related risk factors should be modified to ameliorate bone loss and fracture risk. Cancer preventive measures (smoking cessation and screening programs for cervical cancer) constitute also essential components of the management of these patients.