The article discusses the limitations of traditional microbiological methods in describing microbial diversity and introduces the rRNA approach as a solution. The "Great Plate Count Anomaly" highlights the discrepancy between the number of microorganisms counted visually and those culturable, indicating that many microorganisms are viable but do not form visible colonies. The article emphasizes the importance of uncultured microorganisms, which are often found in symbiotic relationships with other organisms or in unique environments. It outlines the rRNA approach, which involves retrieving rRNA sequence information, designing probes, and performing hybridization to identify and characterize microorganisms without cultivation. This method has been applied to various environments, including symbiotic bacteria and archaea, chemotrophic invertebrates, endosymbiotic bacteria in insects, and pathogenic microorganisms. The article also addresses current obstacles to the general application of the rRNA approach, such as difficulties in sequence retrieval and the formation of chimeric rDNA sequences. Finally, it discusses future perspectives and the potential for increasing the sensitivity of whole-cell hybridization techniques.The article discusses the limitations of traditional microbiological methods in describing microbial diversity and introduces the rRNA approach as a solution. The "Great Plate Count Anomaly" highlights the discrepancy between the number of microorganisms counted visually and those culturable, indicating that many microorganisms are viable but do not form visible colonies. The article emphasizes the importance of uncultured microorganisms, which are often found in symbiotic relationships with other organisms or in unique environments. It outlines the rRNA approach, which involves retrieving rRNA sequence information, designing probes, and performing hybridization to identify and characterize microorganisms without cultivation. This method has been applied to various environments, including symbiotic bacteria and archaea, chemotrophic invertebrates, endosymbiotic bacteria in insects, and pathogenic microorganisms. The article also addresses current obstacles to the general application of the rRNA approach, such as difficulties in sequence retrieval and the formation of chimeric rDNA sequences. Finally, it discusses future perspectives and the potential for increasing the sensitivity of whole-cell hybridization techniques.