Epidemiologic studies have documented substantial increases in the frequency of nodular thyroid disease. This trend is largely due to the increasing detection of nodules by the routine use of sonography in clinical practice. Only a small percentage of the nodules currently being detected will prove to be malignant. The probability of malignancy is similar in nonpalpable and palpable nodules. Fine-needle aspiration cytology has a central role in identifying malignant nodules, which are generally treated with surgery. Most thyroid nodules are cytologically benign and can be managed nonsurgically. Nodules that are completely asymptomatic require follow-up without treatment. Cosmetic problems and/or compression-related symptoms may be indications for surgery. When surgery is contraindicated or refused, several nonsurgical approaches are available. These include levothyroxine therapy, radioiodine treatment, percutaneous ethanol injections, and the new technique of laser photocoagulation. Levothyroxine therapy is the most widely used approach, but its clinical efficacy and safety are controversial. Levothyroxine might, nonetheless, be appropriate in selected cases characterized by low risk for adverse effects and nodule characteristics associated with response to this type of therapy. 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, in our opinion, as the first-line therapy only for recurrent symptomatic cystic nodules. Laser therapy should be reserved for selected patients treated in experienced centers only. With these options, clinicians can personalize the management of nodular thyroid disease according to a careful cost-benefit analysis.