Disease markers are commonly found in complex mixtures that require some form of molecular stratification prior to analysis, and a popular approach is to use specific molecular recognition motifs, antibodies. Achieving precision health objectives will require moving beyond this one-size-fits all approach, and numerous alternatives are being explored. New affinity reagents, such as DNA aptamers, can supplement or even supplant antibodies, targeting therapeutic payloads to tumors, and achieving molecularly specific visualization during surgery. Other alternatives are enabled by innovations in instrumentation, applying proteomics directly to proteins isolated from biofluids in a bias-free way, thus removing molecular recognition agents from the process entirely.