The bacteria most commonly responsible for early-onset (materno-fetal) infections in neonates are group B streptococci, enterococci, Enterobacteriaceae and Listeria monocytogenes. Coagulase-negative staphylococci, particularly Staphylococcus epidermidis, are the main pathogens in late-onset (nosocomial) infections, especially in high-risk patients such as those with very low birthweight, umbilical or central venous catheters or undergoing prolonged ventilation. The primary objective of the paediatrician is to identity all potential cases of bacterial disease quickly and begin antibacterial treatment immediately after the appropriate cultures have been obtained. Combination therapy is recommended for initial empirical treatment in the neonate. In early-onset infections, an effective first-line empirical therapy is ampicillin plus an aminoglycoside (duration of treatment 10 days). An alternative is ampicillin plus a third-generation cephalosporin such as cefotaxime, a combination particularly useful in neonatal meningitis (mean duration of treatment 14 to 21 days), in patients at risk of nephrotoxicity and/or when therapeutic monitoring of aminoglycosides is not possible. Another potential substitute for the aminoglycoside is aztreonam. Triple combination therapy (such as amoxicillin plus cefotaxime and an aminoglycoside) could also be used for the first 2 to 3 days of life, followed by dual therapy after the microbiological results. In late-onset infections the combination oxacillin plus an aminoglycoside is widely recommended. However, vancomycin plus ceftazidime (+/- an aminoglycoside for the first 2 to 3 days) may be a better choice. Teicoplanin may be a substitute for vancomycin. However, the initial approach should always be modified by knowledge of the local bacterial epidemiology. After the microbiological results, treatment should be switched to narrower spectrum agents if a specific organism has been identified, and should be discontinued if cultures are negative and the neonate is in good clinical condition. Penicillins and third-generation cephalosporins are generally well tolerated in neonates. There is controversy regarding whether therapeutic drug monitoring of aminoglycosides will decrease toxicity (particularly renal damage) in neonates, and on the efficacy and safety of a single daily dose versus multiple daily doses of these drugs. Toxic effects caused by vancomycin are uncommon, but debate still exists over the need for therapeutic drug monitoring of this agent. When antibacterials are used in neonates, accurate determination of dosage is required, particularly for compounds with a low therapeutic index and in patients with renal failure. Very low birthweight infants are also particularly prone to antibacterial-induced toxicity.