Antibiotics developed over the past quarter century have greatly improved toxic to therapeutic ratios compared to older agents. This is due to both a wider spectrum of in vitro antibacterial activity and less frequent side effects. In combination with once daily dosing and nearly complete bioavailability of some newer agents, the better risk to benefit ratios have led to empiric antibiotic use in many situations even when bacterial infections are not likely. Many newer antibiotics are not often considered toxic, although their side effects have been documented in medical literature, and several antibiotics that were considered very safe have been removed from the market or their use severely restricted within a relatively short time after their introduction. An understanding of the frequency and mechanism of unintended effects helps physicians minimize them, treat them quickly and effectively when they occur, and even avoid them. Drug interactions and potential adverse effects of β-lactam antibiotics, penicillins, cephalosporins, and carbapenems, are presented.