Since 1997, a few studies have been published suggesting the emergence of clinical isolates of Streptococcus pneumoniae resistant to pristinamycin. Such results were not confirmed by recent studies from different investigators using reference techniques for the determination of susceptibilities, which is in accordance with the low probability of emergence of resistance to this antibiotic in vitro. Discrepancies are encountered with macrolide-resistant strains and may be due to the type of method used for susceptibility testing (agar-diffusion test), the final inoculum used in this technique, or the recent lowering of breakpoint for susceptibility. On the contrary, correlation between reference techniques and commercial galleries using liquid medium is excellent. Despite 35 years of exerting selective pressure, the in vitro activity of pristinamycin remains constant against clinical isolates of S. pneumoniae.