In recent years, many new substances have been synthesized in the domain of beta-lactam antibiotics (penicillins, cephalosporins, monobactams, carbapenems), macrolide antibiotics, and quinolones. Their purpose was to counter the development of resistance to older antibiotics, or to achieve pharmacokinetic ameliorations. However, resistance of clinical relevance has also been observed with these new antibiotics: the effect of all third generation cephalosporins is neutralized by the overproduction of chromosomally encoded cephalosporinases (induction or stable derepression), or by the occurrence of extended-spectrum beta-lactamases. They should be used only with caution against bacteria with possible inducibility. In macrolide antibiotics, poor bioavailability after oral administration can lead to therapeutic failure. The improved pharmacokinetic properties of the new macrolide antibiotics can correct this disadvantage. The generally highly active quinolone antibiotics show diminished activity against grampositive bacteria and Pseudomonas aeruginosa. Careful surveillance of resistance and critical use of the quinolones are essential for the prevention and control of resistance.