Patients with diabetes mellitus (DM) are at high risk for several cardiovascular disorders such as coronary heart disease, stroke, peripheral arterial disease, and congestive heart failure. DM has reached epidemic proportions and its strong association with coronary artery disease is responsible for increased cardiovascular morbidity and mortality. DM patients are characterized by platelet hyperreactivity, which contribute to the enhanced atherothrombotic risk of these subjects. Several mechanisms are involved in the hyperreactive platelet phenotype characterizing DM patients. Furthermore, a large proportion of DM patients show inadequate response to standard antiplatelet treatments and high rate of adverse recurrent cardiovascular events despite compliance with standard antiplatelet treatment regimens. Therefore, new antiplatelet treatment regimens are warranted in DM patients to reduce their atherothrombotic risk. The present manuscript provides an overview on the current status of knowledge on platelet function profiles in patients with DM and therapeutic considerations.