The majority of information regarding pharmacokinetics and pharmacodynamics (the action, properties and elimination of a drug in the body) of antibiotics is based on measurements of the serum and plasma concentrations. Current guidelines for surgical antibiotic prophylaxis have clearly demonstrated appropriate therapeutic levels within blood and serum levels, resulting in low incidence of postoperative bacteremia (bacteria in the blood) and sepsis (infection). Despite this, surgical site infections (SSI) remain the most common postoperative complication, affecting up to 20% of patients undergoing intra-abdominal surgery. Inadequate antibiotic penetration into the tissues of the surgical site, in spite of therapeutic serum levels, results in an environment that is susceptible to pathogens and subsequent infections. Antimicrobial tissue levels are influenced by volume of distribution, regional blood flow and biological properties of tissue. The ability of any drug to reach the tissue of interest is dictated by the relative amount of blood flow to that organ. While lungs and kidneys enjoy a robust blood supply, subcutaneous adipose tissue (fat) (the most frequent site of surgical site infections) receives a small fraction of the cardiac output. Obesity creates an increased volume of distribution, thereby resulting in a greater dilution of antibiotics when compared to non-obese subjects. Moreover, this change in volume of distribution is achieved primarily by increasing the relative amount of poorly perfused adipose tissue. Therefore, it should come as no surprise that obesity is a significant risk factor for surgical site infections.