The authors reviewed the literature evaluating the antibacterial effectiveness of intracanal medicaments used in the management of apical periodontitis. A PICO (problem, intervention, comparison, outcome) strategy was developed to identify studies dealing with calcium hydroxide, phenolic derivatives, iodine-potassium iodide, chlorhexidine, and formocresol. The final inclusion/exclusion criteria eliminated all papers except five that evaluated calcium hydroxide. The total sample size in the included studies was 164 teeth. Microbiologic sampling was performed before endodontic treatment (S1), after instrumentation and irrigation (S2), and after intracanal medication (S3). At S2, 62% of canals were positive. After medication, 27% still showed detectable growth. Of cultures that were positive at S2, 45% were still positive at S3. Most studies did not address issues of culture reversals or false positive and false negative cultures. The main component of antibacterial action appears to be associated with instrumentation and irrigation, although canals cannot be reliably rendered bacteria free. Calcium hydroxide remains the best medicament available to reduce residual microbial flora further.