Patients with systemic lupus erythematosus (SLE) have a high prevalence of abnormal bone metabolism and vitamin D deficiency. Genetic studies have provided the opportunity to determine the specific proteins linking vitamin D to SLE pathology [i.e., major histocompatibility complex (MHC) class II molecules, the vitamin D receptor (VDR), microRNAs (miRNAs), the renin-angiotensin system (RAS), apolipoprotein E (ApoE), liver X receptor (LXR), and toll-like receptors (TLRs)]. Vitamin D also exerts protective effects against SLE through non-genomic factors, such as ultraviolet radiation (UV) exposure, matrix metalloproteinase (MMPs), heme oxygenase-1 (HO-1), the prostaglandins (PGs), cyclooxygenase-2 (COX-2), and oxidative stress. Thus, vitamin D may play a beneficial role in SLE. Moreover, the use of calcitriol or 1α,25-dihydroxyvitamin D(3) is optimal for the treatment of SLE patients because this active form of the vitamin D(3) metabolite can modulate inflammatory cytokine production. However, further investigation into the effects of calcitriol with SLE is warranted.