Evolving clinical needs in infectious diseases and fluctuating healthcare trends, such as changing practice patterns and improved standard-of-care, have moved the need for rapid and more accurate diagnostics to the forefront of clinical microbiology. Laboratory consolidation, along with the shrinking technical workforce, has led to technological advances, including total laboratory automation to maximize efficiency from specimen processing through to results. The increased availability of matrix-assisted laser desorption/ionization time of flight mass spectrometry has revolutionized the clinical microbiology laboratory allowing rapid and sensitive microbial identification, as well as the potential for antimicrobial susceptibility testing and microbial typing. Syndromic molecular panels allow for the rapid detection of a large number of potential pathogens from a single specimen and have improved laboratory efficiency. Combined with antimicrobial stewardship these assays have improved patient care. The moderate complexity of these platforms also provides the potential for on-demand and near patient testing. Several point-of-care platforms are also now available which will help to improve access to healthcare in remote areas. Globally, increasing antimicrobial resistance among gram-negative pathogens challenges both clinicians and laboratorians. Rapid molecular platforms that detect ESBL and carbapenemase genes enhance surveillance. Several companies have either marketed or are in the process of developing, rapid, direct phenotypic antimicrobial susceptibility tests, allowing for targeted therapeutic decisions in less than 24 h. Single molecule technologies are being exploited to enhance enzyme immunoassays to improve C. difficile toxin testing and other diseases. Future technologies, including next-generation sequencing (NGS), will also provide exciting opportunities for fast and accurate species identification, resistance and virulence testing, and monitoring for the emergence and spread of a variety of pathogens. Machine learning and artificial intelligence will optimize diagnostic platforms and bioinformatics. Novel biomarkers and assays that assess host response will direct both diagnostic and therapeutic strategies. These exciting new tools will allow clinical microbiologists to view microbial infections from a new perspective, giving rise to precision medicine that will directly affect the well-being of patients.