Quantitative flow cytometric measurement of protein phosphorylation has been developed into a high-throughput drug screening platform that can be used throughout the drug discovery process. Using phosphoflow cytometry, Krutzik et al. (p 132) studied the effects of compounds from a natural product library on cytokine-induced phosphorylation of multiple proteins in the Jak-Stat signaling pathway in subpopulations of primary immune cells. Shown are several Tetris-inspired (http://www.tetris.com) game pieces depicting library compounds, flow cytometric histograms and scatter plots, dose-response curves, and the structure of the Stat1 protein, together forming a heatmap representation of the screening data and revealing pathway- and cell type-specific inhibitors. Cover art by Erin Boyle based on images provided by Peter O. Krutzik and Garry P. Nolan.