In myelodysplastic syndrome (MDS), neoplastic cells originate in hematopoietic stem cells of the bone marrow, causing dysplasia in multiple cell lines. This may ultimately lead to cytopenia and anemia. MDS generally occurs in patients aged over 60 years, and if left unchecked, it can lead to secondary acute myeloid leukemia (AML), which has a worse prognosis than de novo AML. Hence, it is important to find methods to treat and manage MDS and prevent secondary AML. This review tries to point out the best methods to find out the best possible treatment for MDS, which can lead to its remission or possibly cure and prevent it from progressing into AML. In order to do this, the pathogenesis of MDS is taken into account, and it is clear that the various molecular mutations that lead to the hematologic neoplasms directly affect the different chemotherapy agents that can be used. The different common mutations leading to MDS and secondary AML have been reviewed along with the drugs best inclined to target them. Some mutations lead to a worse prognosis than others, and ongoing mutations can lead to drug-resistant neoplasms. Thus, drugs targeting the mutations need to be used. The feasibility of an allogeneic stem cell transplant is also taken into account, as this can lead to a total cure of MDS. Methods of decreasing post-transplant recovery time and complications have been looked into, and more studies need to be done on the matter. Currently, it is clear that a more personalized approach to each individual case with its own set of drug combinations is the best approach to treating MDS and secondary leukemia and increasing the overall survival (OS).