Surface-enhanced Raman spectroscopy (SERS) is a powerful biosensing technique that combines molecular fingerprint specificity with high sensitivity, detecting trace amounts using plasmonic-based metallic nanostructured sensor platforms. SERS strategies include direct and indirect, as well as targeted and untargeted methods, depending on sample complexity and target analyte affinity. The development of SERS platforms, such as microfluidic environments, lab-on-a-fiber approaches, and paper-based immunoassays, aims at creating portable systems for point-of-care use in clinical and non-lab settings. Combining SERS with other techniques enhances measurement conditions, miniaturization, and sensitivity. This review summarizes key analytical applications of SERS in biosensing, including medicine, clinical diagnostics, environmental monitoring, food quality assessment, and biological studies.