Tissue concentration describes the concentration of a drug in a tissue without specifying the pharmacological compartment of the tissue. For a drug to be able to treat a specific infectious disease it is necessary that the drug is available at the site of infection. Tissues are made of distinct pharmacological compartments (interstitial fluid, cells, and within cells the various subcellular organelles) in which the drug is usually not distributed equally. Therefore, commonly used measurements in tissue homogenates are not informative with respect to the (active) concentration of the antimicrobial at the site of infection. Since most bacterial infections are located in the extracellular compartment, these concentrations are of primary interest. If a compound is distributed mainly extracellularly, such as β-lactams and aminoglycosides, grinding up the tissue means dilution of the drug by mixing intracellular and extracellular fluids, resulting in an underestimation of its concentrations at the site of infection. Conversely, if drugs are accumulated by cells (such as fluoroquinolones or macrolides), assay of total tissue levels will lead to a gross overestimation of the extracellular concentration. The opposite is true for intracellular infections.