Myelodysplastic syndromes (MDS) are a complex group of clonal hematopoietic disorders with an attendant diverse array of associated genetic changes. Conventional cytogenetics plays a prominent and well-established role in determining the contemporary diagnosis and prognosis of these disorders. More recently, molecular approaches have been useful in further characterizing this group of diseases, albeit in a largely experimental context, with the detection of changes at the single gene level including mutations, amplification and epigenetic phenomena. Nevertheless, we remain largely ignorant of the genetic underpinnings of MDS. Here we briefly review the established role of cytogenetics in MDS, and emphasize recent advances in unraveling the genetics of MDS, with a view towards how such findings might facilitate our ability to understand, diagnose and treat these disorders in a more rational manner.