Systems Biology Single-cell DNA and RNA sequencing can describe numerous aspects of cell state, but such techniques cannot assess the functional effectors of cells: proteins. In a Perspective, Slavlov discusses the advances in single-cell mass spectrometry techniques that allow protein profiling, including characterization of protein modifications and potentially complex composition and subcellular localization. Although there are limitations to this emerging technology, single-cell proteomics may add to the characterization of cellular components and provide functional information about signaling networks in homeostasis and disease. Science , this issue p. [512][1] [1]: /lookup/doi/10.1126/science.aaz6695