Gram-negative bacillary meningitis is being diagnosed more frequently, and the introduction of newer β-lactam antibiotics has contributed significantly to successful therapy. These new agents—because of their ease of administration and relative safety—also allow nonspecialists to treat the disease. There are, however, pitfalls in therapy of infections due to this heterogenous group of organisms. Extremely susceptible organisms, such as Escherichia coli and Klebsiella pneumoniae, most often respond to cephalosporin monotherapy, whereas relatively resistant organisms such as Acinetobacter and some Enterobacter may not. In these cases, combination therapy with an aminoglycoside is warranted. Testing the infecting organism for antibiotic susceptibility at the appropriate inoculum and pH may be useful in predicting therapeutic outcome.