As I?3-adrenoceptor agonists metamorphose from experimental tools into therapeutic drugs, it is vital to obtain a comprehensive picture of the cell and tissue functions mediated by this receptor subtype in humans. Human tissues with proven functions and/or a high expression of I?3-adrenoceptors include the urinary bladder, the gall bladder, and other parts of the gastrointestinal tract. While several other I?3-adrenoceptor functions have been proposed based on results obtained in animals, their relevance to humans remains uncertain. For instance, I?3-adrenoceptors perform an important role in thermogenesis and lipolysis in rodent brown and white adipose tissue, respectively, but their role in humans appears less significant. Moreover, the use of tools such as the agonist BRL 37344 and the antagonist SR59230A to demonstrate functional involvement of I?3-adrenoceptors may lead in many cases to misleading conclusions as they can also interact with other I?-adrenoceptor subtypes or even non-adrenoceptor targets. In conclusion, we propose that many responses attributed to I?3-adrenoceptor stimulation may need re-evaluation in the light of the development of more selective tools. Moreover, findings in experimental animals need to be extended to humans in order to better understand the potential additional indications and side effects of the I?3-adrenoceptor agonists that are beginning to enter clinical medicine.