The introduction of several new drug groups into the treatment of type 2 diabetes in the past few decades leads to an increased requirement for an individualized treatment approach. A personalized treatment is important from the point of view of both efficacy and safety. Recent guidelines are based mainly on entirely phenotypic characteristics such as diabetes duration, presence of macrovascular complications, or risk of hypoglycemia with the use of individual drugs. So far, genetic knowledge is used to guide treatment in the monogenic forms of diabetes. With the accumulating pharmacogenetic evidence in type 2 diabetes, there are reasonable expectations that genetics might help in the adjustment of drug doses to reduce severe side effects, as well as to make better therapeutic choices among the drugs available for the treatment of diabetes.