Invasive non-meningeal pneumococcal infections remain a major cause of morbidity and mortality worldwide. The factors affecting the epidemiology and mortality of pneumococcal infections are discussed. The increase and spread of resistance to antimicrobial agents among pneumococci is a cause of concern to the clinician. There are links between the usage of antibacterial agents and the development of resistance. Resistance to penicillin and other beta-lactams has become widespread but this does not appear to have decreased the efficacy of some of these agents against non-meningeal infections. There is evidence that the good pharmacokinetic and pharmacodynamic features of the third generation cephalosporins (cefotaxime and ceftriaxone) contribute to their efficacy in vivo. New breakpoints for cefotaxime and ceftriaxone against non-meningeal pneumococcal isolates were proposed by the National Committee for Clinical Laboratory Standard (NCCLS, US), based on the clinical evidence of the efficacy of these drugs. In contrast there is increasing evidence that resistance to macrolides can lead to a poor clinical response. Fluoroquinolones have been widely used to treat respiratory tract infections among others, and pneumococcal resistance to these agents in vitro, although currently low, is increasing. There are reports that resistance to fluoroquinolones can develop during treatment and may be reflected in a lack of clinical response. Several clinical and epidemiological variables (e.g. prior antibiotic use) can be useful to identify patients at risk from infections with antibiotic-resistant pneumococci. These patients would be those who would benefit the most from a pneumococcal vaccination programme.