Levothyroxine therapy is used in case of deficiency of the thyroid hormones in the human organism. Many conditions, either physiological or paraphysiological or clearly pathological, can alter the levothyroxine absorption in the human body. Levothyroxine absorption can indeed be impaired by age, patient's compliance, fasting, the intake of certain foods (such as dietary fibers, grapes, soybeans, papaya and coffee) or by some drugs (such as proton-pump inhibitors, antacids, sucralfate, et cetera). Additionally, many gastrointestinal diseases, such as the conditions that disrupt the integrity of the intestinal barrier and the diseases that impair gastric acidity, may alter the bioavailability of levothyroxine. Since the enormous, widespread diffusion of thyroid diseases, a large number of patients have to face such issues. Therefore, the development of new levothyroxine oral formulations, other than solid tablets, may represent an interesting therapeutic approach, at the same time simple and effective, to face this problem. Recently, two different levothyroxine formulations have been proposed: the liquid formulation and the softgel formulation. Such formulations represent an innovative, effective and cheap therapeutic approach to hypothyroid patient with problems of impaired absorption of levothyroxine.