The AFTN was established as a clinical entity by the 1918 report of Goetsch, correlating cellular mitochondrial content with nodular function, and showing the inverse correlation between AFTN function and extranodular tissue function. Degeneration, common in AFTNs, can preclude development of hyperthyroidism, eliminate hyperthyroidism, or even induce transient spontaneously resolving hyperthyroidism. AFTNs are nearly always benign. Most reports of malignant AFTNs are inadequately documented. Whether AFTNs are toxic can be determined by clinical evaluation, with laboratory confirmation using principally serum T3 assays and TRH testing. Whether warm nodules are AFTNs may be determined by suppression imaging. Nontoxic AFTNs are usually observed. For older patients with borderline high serum T3 levels, blunted responses to TRH, or subnormal responses on supersensitive TSH assays, prophylactic therapy may be prudent. Toxic AFTNs may be treated surgically (patients younger than 40) or with radioactive iodine (older patients). High dose radioactive iodine therapy is preferred because it more consistently ablates AFTN function.