Introduction: Patients with systemic lupus erythematosus (SLE) have a better survival than decades ago; nevertheless, they still experience a low health-related (HR) quality of life (QoL). Areas covered: After defining QoL and HRQoL, we review the need to assess it, its elements, how to measure it, its predictors, and its impact and potential interventions to improve it. Expert commentary: Physicians assessments of disease activity and damage do not capture the patients’ perspective of their health, and these differences could lead to nonadherence to therapy. Based on that, a comprehensive evaluation of SLE should include the assessment of HRQoL or the sum of the physical, psychological, and social perception of wellbeing, influenced by the patient’s illness. The most consistent predictors of low HRQoL are older age, poverty, lower educational level, behavioral issues, some clinical manifestations, and comorbidities. HRQoL impacts negatively on dealing with stress, intimal relationship, home and job-related activities, and treatment adherence. At the present, there are no successful specific therapeutic strategies aimed at improving it.