In 2005 the Australian Group for Antimicrobial Resistance (AGAR) conducted a survey of the prevalence of antimicrobial resistance in unique clinical isolates of Streptococcus pneumoniae. Twenty laboratories from the 5 mainland states and the Australian Capital Territory collected 1,776 isolates prospectively and tested them by disk diffusion, Etest and/or agar dilution against a range of antimicrobials. Data from this survey were compared with AGAR surveys conducted in 1989, 1994, 1999 and 2002. Non-susceptibility to penicillin was detected in 28.0% of isolates, 22.7% were erythromycin resistant, 15.6% clindamycin resistant, 18.4% tetracycline resistant and 31.0% trimethoprim-sulphamethoxazole resistant. Levofloxacin resistance was detected in only 4 of 1,775 (0.2%) isolates tested. Intermediate resistance to levofloxacin was detected in another 4 isolates. Moxifloxacin resistance was present in 2 isolates with minimum inhibitory concentrations of 3 mg/L and 4 mg/L. Seventeen point three per cent of isolates were multi-resistant (acquired resistance to more than 2 drug classes). Trend data show an increase in penicillin non-susceptible strains in each survey from 1989 to 2005. Between 1999 and 2005 the proportion of invasive strains with high-level resistance increased from 2.6% to 5.4%. After a rapid emergence and rise in resistance between 1989 and 1999, recent studies have documented a continuing rise in resistance to all non-beta-lactams except trimethoprim-sulphamethoxazole.