The myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid disorders characterised by impaired peripheral blood cell production due to bone marrow dysplasia affecting one or more of the major myeloid cell lines. MDS are one of five major categories of myeloid neoplasms according to the World Health Organization (WHO) classification system for haematological cancers. Given their cytological and cytogenetic heterogeneity, these diseases probably constitute a group of molecularly distinct entities with variable degrees of ineffective haematopoiesis and susceptibility to leukaemic transformation. Recent studies provide some insights into the physiopathology of MDS. In the early stages, one mechanism contributing to hypercellular marrow and peripheral blood cytopenia is a significant increase in programmed cell death (apoptosis) in haematopoietic cells. Furthermore, altered responses in relation to cytokines, the immune system and bone marrow stroma also contribute to the disease phenotype. Deletions of chromosome 5q31-q32 are the most common recurring cytogenetic abnormalities detected in MDS. The 5q- syndrome is a new entity recognised in the WHO classification since 2001 and is associated with a good prognosis. Haploinsufficiency of multiple genes mapping to the common deleted region at 5q31-32 may contribute to the pathogenesis of 5q- syndrome and other MDS with 5q- deletion. Many studies have demonstrated that altered DNA methylation and histone acetylation can alter gene transcription. Abnormal methylation of transcription promoter sites is universal in patients with MDS, and the number of involved loci is increased in high-risk disease and secondary leukaemias. A better understanding of the pathogenesis of MDS can contribute to the development of new treatments such as hypomethylating drugs, immunomodulatory agents such as lenalidomide, and immunosuppressive drugs aimed at reversing the specific alteration that results in improvement in patients with MDS.