Thyroid nodules are frequently diagnosed today, mainly due to the wide use of neck ultrasonography (US). The majority of these lesions are benign; suspicion for malignancy is an indication for surgery, while benign thyroid nodules may be managed conservatively. There is evidence that a large percentage of patients with thyroid nodules are over-treated. Careful and accurate identification of patients with thyroid nodules that are highly suspicious for an underlying malignancy would allow for a more reasonable therapeutic approach and would result in a reduction of the number of unnecessary thyroidectomies. Fine needle aspiration cytology is currently the most accurate and cost effective diagnostic approach for the evaluation of patients with nodular thyroid disease. Completely asymptomatic nodules require follow-up without treatment. Cosmetic problems or compression related symptoms may be indications for surgery. When surgery is contraindicated or refused, several non-surgical approaches are available. These include levothyroxine therapy, radioiodine treatment, injection of percutaneous ethanol and laser photocoagulation. Levothyroxine therapy is the most widely used approach, but its clinical efficacy and safety are controversial. Treatment with radioiodine is the therapy of choice for toxic nodules or for symptomatic nodular goiters when surgery is not possible. Percutaneous ethanol injection should be used as the first-line therapy for recurrent symptomatic cystic nodules. Laser therapy should be reserved only for selected patients treated in experienced centers. With these options, clinicians can personalize the management of nodular thyroid disease according to a careful cost benefit analysis.