Recording the state and dynamics of intracellular signaling networks in clinical specimens can help identify and validate biomarkers, but may also prove useful in developing and monitoring targeted therapies. Studying cell signaling on a system-wide level in solid tissue, however, is often not feasible using mass spectrometry, because this technique generally requires relatively large sample quantities. A number of promising miniaturized proteomic technologies have emerged, which circumvent these limitations and offer the ability to monitor protein abundances and posttranslational modification states in a multiplexed and quantitative fashion. These technologies have the potential to accelerate molecular diagnostics and therapeutics, and may ultimately facilitate the broad adoption of personalized approaches to patient management and treatment.