The current trend of therapy requires the use of antibiotics, which combine a high level in vitro antibacterial activity with the capacity to act in concert with the immune system in a way that potentiates the hosts defence mechanisms. Whilst such additional effects on the immune system by the antibiotic may be of secondary importance in patients with normal host defence mechanisms, they are of primary importance in patients with depression of the immune system, who are highly susceptible to infections, often difficult to treat, even with the current and modern antimicrobial agents. This investigation delineates our own results regarding the impact of some antimicrobial agents such as the most recent β- lactams, carbapenems, trinems, glycopeptides, quinolones, aminoglycosides and macrolides upon the primary functions of phagocytes, namely human polymorphonuclear granulocytes and macrophages. The ability of the above mentioned drugs to penetrate human phagocytes and their consequences upon subsequent phagocytic ingestion and killing of ingested bacteria, both Gram-positive and Gram-negative, are here reported. Moreover the influence exerted by some of these antibiotics either on phagocytic functions or on the release of cytokines is illustrated. The beneficial properties of some b-lactams, which result in “restoring” the depressed phagocyte-dependent response in patients on chronic hemodialysis or in renal transplant recipients, are also focused.