Analytical technologies that can improve disease diagnosis are highly sought after. Current screening/diagnostic tests for several diseases are limited by their moderate diagnostic performance, invasiveness, costly and laborious methodologies or the need for multiple tests before a definitive diagnosis. Spectroscopic techniques, including infrared (IR) and Raman, have attracted great interest in the medical field, with applications expanding from early disease detection to monitoring and real-time diagnosis. This review highlights applications of IR and Raman spectroscopy, with a focus on cancer and infectious diseases since 2015, and underscores the diverse sample types that can be analyzed, such as biofluids, cells and tissues. Studies involving more than 25 participants per group (disease and control group; if no control group >25 in disease group) were considered eligible, to retain the clinical focus of the paper. Following literature searches, we identified 94 spectroscopic studies on different cancers and 30 studies on infectious diseases. The review suggests that such technologies have the potential to develop into an objective, inexpensive, point-of-care test or facilitate disease diagnosis and monitoring. Up-to-date considerations for the implementation of spectroscopic techniques into a clinical setting, health economics and successful applications of vibrational spectroscopic tests in the clinical arena are also discussed.