The ultimate goal in antibiotic treatment of acute otitis media (AOM) is eradication of the pathogens from the middle ear fluid (MEF). To test the ability of an antibiotic to achieve this goal, the best available method is to obtain MEF by aspiration before initiating antibiotics and to repeat this procedure during treatment, a method which was termed the 'in vivo sensitivity test'. This advantageous method is difficult to perform and thus only a few groups were able to conduct such large-scale studies. The available information is discussed in the present manuscript, as well as some preliminary results suggesting that oral beta-lactam antibiotics may not be the ideal drugs to date, due to the emergence of resistant pneumococci.