Medication nonadherence has not been well characterized in systemic lupus erythematosus (SLE). Our objective was to a conduct a systematic review of the literature, examining the burden and determinants of medication nonadherence in SLE. We conducted a systematic search of Medline (1946-2015), Embase (1974-2015), and Web of Science (1900-2015) databases and selected original studies of SLE patients that evaluated nonadherence to SLE therapies as the primary study outcome. We extracted information on study design, sample size, length of followup, data sources, type of nonadherence problem examined, adherence measures and reported estimates, and determinants of adherence reported in multivariable analyses. After screening 4,111 titles, 11 studies met the inclusion criteria. Study sample sizes ranged from 32 to 246 patients, and studies were categorized according to data source: self-report (5), electronic monitoring devices (1), clinical records from rheumatology clinics (3), and refill information from pharmacy records (2). Overall, the percentage of nonadherent patients ranged from 43% to 75%, with studies consistently reporting that over half of patients are nonadherent. Studies also showed that up to 33% of patients discontinue therapy after 5 years. Determinants of nonadherence included having depression, rural residence, lower education level, and polypharmacy. Overall, synthesis of current evidence suggests that the burden of medication nonadherence is substantial in SLE. Findings highlight the importance of developing interventions to support adherence and improve outcomes among patients.