The size of cells, tissues and organisms is a fundamental yet poorly understood attribute of biological systems. Traditional difficulties in interrogating the basis for size regulation have been surmounted by recent systematic phenotypic analyses. Genome-wide size screens in yeast suggest that ribosome biogenesis rate dictates cell size thresholds, whereas analogous RNAi-based size screens in metazoans cells reveal further connections between cell size and translation, as well as myriad other pathways. Sophisticated genetic screens in flies have delineated the new Hippo-signalling pathway that controls tissue and organ size. While the plethora of genes that alter size phenotypes at present defies a unified model, systems-level analysis suggests many new inroads into the longstanding enigma of size control.