The myelodysplastic syndromes (MDS) share an origin in the hematopoietic stem cell but have otherwise very heterogeneous biological and genetic characteristics. Clinical features are dominated by cytopenia and substantial risk for progression to acute myeloid leukemia. According to the World Health Organisation (WHO) MDS is defined by cytopenia, bone marrow dysplasia, and by certain karyotypic abnormalities. The understanding of disease pathogenesis has undergone major development with the implementation of next generation sequencing, and a closer integration of morphology, cytogenetics and molecular genetics is currently paving the way for improved classification and prognostication. True precision medicine is still in the future for MDS and the development of novel therapeutic compounds with a propensity to markedly change patient outcome lags behind many other blood cancers. Treatment of higher-risk MDS is dominated by monotherapy with hypomethylating agents but novel combinations are currently being evaluated in clinical trials. Erythropoietic agents (ESAs) continue to be first-line treatment for the anemia of lower-risk MDS but luspatercept has shown promise as second-line therapy for sideroblastic MDS and lenalidomide is established second-line treatment for del(5q) lower-risk MDS. The only potentially curative option for MDS is hematopoietic stem cell transplantation, until recently associated with a relatively high risk for transplant-related mortality and relapse. However, recent studies show increased cure rates due to better tools to target the malignant clone with less toxicity. This review provides a comprehensive overview of the current status of the clinical evaluation, biology and therapeutic interventions for this spectrum of disorders.