Acne vulgaris is a common chronic dermatologic disorder that affects both physical appearance and mental well-being. The disease presents with comedones, inflammatory papules, pustules, and nodulocystic lesions. Clinicians use various treatment modalities, including topical agents, systemic therapies, procedural interventions, and lifestyle or dietary modifications. Among these options, isotretinoin remains the most effective therapy. For nearly 40 years, clinicians have prescribed isotretinoin and achieved high efficacy in managing moderate-to-severe acne. However, the drug frequently causes adverse effects involving multiple organ systems. Standard treatment protocols recommend a dosage of 0.5–1 mg/kg/day for 4–6 months, targeting a cumulative dose of 120–150 mg/kg. In recent years, researchers have increasingly investigated low-dose isotretinoin and demonstrated comparable efficacy to the standard regimen, with fewer adverse effects and higher patient satisfaction. However, investigators have not yet established a consistent definition of “low dose” across studies. Although numerous international studies have evaluated low-dose isotretinoin, researchers in Vietnam have published limited data on this regimen. This article provides clinicians with a clearer perspective on the role of low-dose isotretinoin in acne treatment and relapse management. It also summarizes updated evidence regarding its safety and therapeutic effectiveness. Although current evidence does not yet support formal inclusion in treatment guidelines, growing clinical interest and ongoing research highlight low-dose isotretinoin as a promising strategy. This approach may optimize therapeutic outcomes, reduce adverse effects, and improve patient satisfaction in acne management.