<p>The majority of the prokaryotic microorganisms, especially bacteria cannot be cultivated under laboratory conditions. Irrespective of environmental samples, direct count of prokaryotes always exceeds viable count, a condition popularly coined as “Great Plate count anomaly”. Our inability to culture them in isolation under laboratory conditions is due to many reasons. One possible reason could be the existence of a special group of extremophilic bacteria, such as, oligophilic bacteria, a group, that loves to grow in nutrient-deficient conditions. They are slow growing, showing unique physiological adaptations that help them to thrive in nutrient-deficient conditions. Most of them are small in size, with high-affinity nutrient uptake systems, and specialized metabolic pathways that differentiate them from other groups of bacteria. However, these different adaptations can pose obstacles to their cultivation in laboratory conditions where conventional culture media are used. Different methods are used for their isolation including dilution-to-extinction plating methods. The physiological and molecular mechanisms that support oligophilic adaptation at the genomic and regulatory levels have been documented with respect to model bacteria, such as <i>Candidatus Pelagibacter ubique</i> and <i>Sphingopyxis alaskensis.</i> Furthermore, ecological significance and biotechnological potential of this group have been highlighted. They can be a resource for novel gene pools, antimicrobials and metabolic pathways. The “Great Plate Count Anomaly” is still a harsh reality and the study of oligophilic bacteria might reduce the gap between the unknown majority and known minority.</p>