Fine-needle aspiration (FNA) biopsy of thyroid nodules is minimally invasive and safe and is usually performed on an outpatient basis. However, the optimal application of FNA requires not only technical skill but also an awareness of the limitations of the procedure, the indications for its use, the factors that affect the adequacy of the biopsy specimen, and the postprocedural management strategy. Ultrasonographic (US) features that are considered indications for FNA include single and multiple thyroid nodules. The results of FNA biopsy are operator dependent. In addition, the results may be affected by the lesion characteristics, the accuracy of lesion and needle localization, the method of guidance, the number of aspirated samples, the needle gauge, the aspiration technique, and the presence or absence of on-site facilities for immediate cytologic examination. With regard to postprocedural management, nodules that are diagnosed as benign on the basis of an adequate FNA specimen should be monitored with follow-up US. Circumstances that necessitate repeat FNA include sample inadequacy, nodule enlargement, cyst recurrence, or clinical or imaging findings that arouse suspicion about the presence of a malignancy even when cytologic findings in the biopsy specimen indicate benignity. Supplemental material available at radiographics.rsnajnls.org/cgi/content/full/28/7/1869/DC1.