This article establishes the pharmacokinetic-pharmacodynamic parameters that are important when considering the intracellular activity of antibiotics. Generally speaking, the main classes of antibiotics seem to share globally the same properties against extracellular and intracellular organisms. The specific cellular pharmacokinetic properties may modulate those parameters so as to let other ones to become critical. Simple rules, such as equating accumulation and activity, are certainly incorrect, and other determinants need to be added to the equation. Finally, this article emphasizes the fact that much remains to be done in this area before rational therapeutic choices can be made.