Postpartum depression (PPD) is defined as the onset of major depressive disorder in mothers, occurring during pregnancy or within 4 weeks post-delivery. With 7% of pregnancy-related death in the United States owing to mental health conditions, including PPD, and a global prevalence of 12%, PPD is a growing public health concern. In 2019, the Food and Drug Administration (FDA) approved brexanolone, an exogenous analog of allopregnanolone, as the first ever drug to be specifically indicated for treating patients with PPD. This approval was preceded by an open-label study and three randomized placebo-controlled trials, each assessing the safety, tolerability, and efficacy of brexanolone, using mean Hamilton Rating Scale for Depression (HAM-D) score reduction as the primary outcome. In each randomized controlled trial, the drug was administered as an intravenous infusion given over 60 h. Enrolled participants were followed up on days 7 and 30 to evaluate the sustained effect. A statistically significant reduction in mean HAM-D score compared to placebo was observed in all three studies, supporting brexanolone’s use in treating moderate-to-severe PPD. Therefore, this article attempts to briefly review the pharmacology of brexanolone, evaluate the latest available clinical data and outcomes concerning its use, reevaluate its position as a ‘breakthrough’ in managing PPD, and review the cost-related barriers to its worldwide standardized use.