Myelodysplastic syndromes are associated with a risk of severe infections. While neutropenia is likely the main predisposing factor, several other immune defects have been reported, including impaired neutrophil function, B-, T-, and NK-cell defects and the possible consequences of iron overload due to red blood cell transfusions. The advanced age of most patients, their frequent comorbidities and the fact that drugs like hypomethylating agents and lenalidomide, which are effective in myelodysplastic syndromes but can transiently worsen neutropenia, may increase the risk of infection and their severity in this context. A majority of infections in myelodysplastic syndromes are bacterial, while the incidence of fungal infections is not well known and viral infections seem to be rare. No prophylactic measures of infections have demonstrated efficacy in myelodysplastic syndromes. However, pending more data, we propose here some recommendations for the management of patients with myelodysplastic syndromes. In the future, value will be provided by prospective trials testing the efficacy of prophylactic and therapeutic approaches of infection in these patients, especially in the context of new drugs available in myelodysplastic syndromes.