Hypothyroidism may occur as a result of primary gland failure or insufficient thyroid gland stimulation by the hypothalamus or pituitary gland. Hypothyroidism may be associated with pernicious anemia as part of the autoimmune polyglandular endocrinopathy. Thyroid hormones (THs) influence endothelium and directly raise NO production in vascular smooth muscle cells through the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. Folic acid deficiency, administration of folate antagonists such as methotrexate and carbamazepine and disturbance of methionine metabolism after hypothyroidism has been suggested as the reasons of rising in serum homocysteine levels. The following article reviewed association of serum vitamin B12, folic acid and nitrosative stress in hypothyroidism. It suggests that combination therapy with levothyroxine plus folic acid will diminish serum homocysteine level more effectively; so this treatment regimen is preferable to levothyroxine alone in hypothyroidism.