The detection of biomarkers is critical for enabling early disease diagnosis, monitoring the progression, and tracking the effectiveness of therapeutic intervention. Plasmonic sensors exhibit a broad range of analytical capabilities, from the rapid generation of colorimetric readouts to single-molecule sensitivity in ultralow sample volumes, which have led to their increased exploration in bioanalysis and point-of-care applications. This perspective presents selected accounts of recent developments on the different types of plasmonic sensing platforms, the pervasive challenges, and outlook on the pathway to translation. We highlight the sensing of upcoming biomarkers, including microRNA, circulating tumor cells, exosomes, and cell-free DNA, and discuss the opportunity of utilizing plasmonic nanomaterials and tools for biomarker detection beyond biofluids, such as in tissues, organs, and disease sites. The integration of plasmonic biosensors with established and upcoming technologies of instrumentation, sample pretreatment, and data analysis will help realize their translation to clinical settings for improving healthcare and enhancing the quality of life.