Diabetes mellitus is one of the most common endocrine disorders. It affects almost 6% of the world’s population, and its prevalence continues to increase. The causes of diabetes mellitus are multifactorial, and in the general population both genetic and environmental factors contribute evenly to its development. Several genes have been consistently associated with type 2 diabetes mellitus; however, it is not clear how many of those translate into increased cardiovascular disease risk. Recent evidence suggests that genetic variation at the CALPN10, FABP4, GK, GST, PPARA, and PPARG loci may confer higher cardiovascular disease risk in patients with type 2 diabetes mellitus. However, the evidence is scattered and inconclusive and its translation into practical clinical testing will require studies properly designed to examine not only simple genetic associations but also gene-gene and gene-environment interactions.