Systemic lupus erythematosus (SLE) is a chronic multisystem disease and despite the improvements in treatment, long-term care still represents a clinical challenge. Previous long-running studies have demonstrated a continuous improvement in mortality and this trend has persisted over the last two decades. However, there still remains a significantly increased mortality in comparison to the normal population. Besides deaths caused by disease activity, cardiovascular and infectious diseases also play a major role. While deaths caused by SLE activity or infections have declined over the years, there has been a notable increase in cardiovascular diseases. As the improvement of SLE activity and infections can be traced back to individually optimized treatment regimes and the more cautious use of steroids, the cardiovascular complications are due to accelerated atherosclerosis and the improved survival with ageing of the patients. This long-term aspect needs to be taken into account in the early stages of disease when treating disease activity and comorbidities.