Image-based approaches to single-cell transcriptomics are emerging as powerful complements to single-cell RNA sequencing, in part, because these techniques preserve the native spatial context of RNAs within cells and tissues. I will describe multiplexed error robust single-molecule fluorescence in situ hybridization (MERFISH)—a technique capable of imaging thousands of different RNAs simultaneously in fixed cells—and its use for the discovery and mapping of cell types within intact tissues.