A majority of patients with lower-risk myelodysplastic syndrome (MDS) will present with or develop anemia. Anemia in MDS is associated with decreased quality of life and may correlate with decreased progression-free survival and overall survival. In this state of the art review we summarize current risk stratification approaches to identify lower-risk MDS (LR-MDS), the natural history of the disease, and meaningful clinical endpoints. The treatment landscape of LR-MDS with anemia is also rapidly evolving; we review the role of supportive care, erythropoietin stimulating agents, lenalidomide, luspatercept, hypomethylating agents (HMAs), and immunosuppressive therapy (IST) in the management of LR-MDS with anemia. In patients with deletion 5q (del5q) syndrome lenalidomide has both efficacy and durability of response. For patients without del5q who need treatment, the management approach is impacted by serum erythropoietin (EPO) level, SF3B1 mutation status, and ring sideroblast status. Given the data from the Phase III COMMANDS trial, we utilize luspatercept in those with SF3B1 mutation or ring sideroblasts that have an EPO level < 500 U/L; in patients without an SF3B1 mutation or ring sideroblasts there is equipoise between luspatercept and use of an erythropoietin stimulating agent (ESA). For patients who have an EPO level ≥ 500 U/L or have been previously treated there is not a clear standard of care. For those without previous luspatercept exposure it can be considered particularly if there is an SF3B1 mutation or the presence of ring sideroblasts. Other options include HMAs or IST; the Phase III IMERGE trial supports the efficacy of the telomerase inhibitor imetelstat in this setting and this may become a standard option in the future as well.