Noble-metal nanoparticles (NMNPs) have unique properties beneficial for the development of novel reporting technologies to enhance the detection sensitivity and specificity of clinically validated biomarkers. Unique size-and shape-dependent optical, catalytic, and magnetic properties of NMNPs have enabled significant advances in biosensing due to facilitation of colorimetric detection, localized surface plasmon resonance, fluorescence enhancement/quenching, surface-enhanced Raman scattering, electrochemical activity, etc. Among these, the colorimetric detection method is highly attractive for use in point-of-need diagnostic applications in which color changes in the presence of biomarkers can be directly observed with the naked eye without the requirement of any equipment. This capability fulfills one of the main requirements set by the World Health Organization to provide people living in remote/regional/low-resource settings access to effective and comprehensive primary care. Although there are many scientific publications, the commercialization of NMNP-based colorimetric diagnostic assays for point-of-need applications is lagging mainly because of the lack of knowledge related to NMNPs in dealing with biological samples and sensitivity of the tests required for the real-world applications. Herein, we provide a critical review of the fundamentals of NMNPs and the recent progress in their usage for monitoring and detecting clinically relevant biomarkers in biological samples at the point-of-need to scientifically assess the benefits and limitations of this technology. We then compare the methods employed to enhance the sensitivity of colorimetric assays in detecting clinically validated target biomarkers in body fluids. Finally, we investigate the future trends and strategies that deserve more research to increase the successful commercialization of these assays.