Infectious disease experts and public health officials continue to warn the medical community and the public that more strains of respiratory tract pathogens are becoming resistant to the antibiotics commonly used to eradicate them. The inappropriate use of antibiotics to treat viral infections has contributed to the development of multidrug resistance in the 3 key bacterial pathogens that cause respiratory tract infections: Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Traditionally, susceptibility of pathogens to antibiotics has been evaluated with in vitro testing by minimum inhibitory concentration (MIC) determination, which has also been used to establish breakpoints between susceptible and resistant organisms based on MIC distributions. However, a more clinical approach has been developed based on the correlation of pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobials with MICs and clinical studies, thereby establishing the new concept of PK/PD breakpoints. New guidelines for outpatient management of respiratory tract infections have been based on PD parameters.