Identification and characterization of micro-organisms that cause infections are crucial for successful management of patients. For several decades, routine clinical microbiological diagnostic laboratories have been equipped with a growing panel of culture-dependent and culture-independent methods to investigate the microbial etiology of infectious diseases. Considering the disadvantages of traditional methods, multiplex PCR techniques have been routinely endorsed in clinical microbiology laboratories as rapid and sensitive diagnostic and prognostic tool including many PCR panels routinely used in microbial diagnostics. The great advance in medical biotechnology has been associated with development of Matrix-Associated Laser Desorption Ionization Time of Flight Mass Spectrometry (MALDI TOF MS). The power of MALDI TOF MS correctly identified 93.2% of organisms to the species level and 5.3% to the genus level. Recently, the application of next-generation sequencing (NGS) technology and its various methodological variants makes it possible to detect different types of microorganisms present within a microbial sample simultaneously, using a culture-independent approach and in a single sequencing run. Over the next 5 to 10 years, although it is unlikely to see NGS completely replacing the conventional culture and susceptibility methods, a wealth of NGS applications will be acquired in the vast majority of diagnostic microbiology laboratories worldwide, providing enhanced diagnostic capabilities and improving the quality of patients care. In Egyptian diagnostic microbiology laboratories, we have to ask ourselves; are we ready to subsist this new era? Sure the answer is: ‘All things are ready, if our mind be so'.