Abstract: Patients with severe infections often suffer from systemic inflammatory responses that induce pathophysiological disturbances. These disturbances significantly alter the pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobial agents, severely compromising the efficacy of anti-infective therapies and posing substantial challenges to rational clinical medication. This review systematically summarizes the variation characteristics of key PK parameters in such patients, including clearance rate, distribution volume, absorption process and tissue permeability. It focuses on the strategies optimizing the antibiotics therapy, such as setting individualized PK/PD targets, adjusting loading dose and administration methods, and achieving precise dosage control through therapeutic drug monitoring. The comprehensive use of above programs aims to improve the precision and effectiveness of the antimicrobial therapy for the patients with severe infections so as to provide guidance for reasonable clinical use of antibiotics and improvement of prognosis of the patients.