Motivation As part of the NIH Library of Integrated Network-based Cellular Signatures program, hundreds of thousands of transcriptomic signatures were generated with the L1000 technology, profiling the response of human cell lines to over 20 000 small molecule compounds. This effort is a promising approach toward revealing the mechanisms-of-action (MOA) for marketed drugs and other less studied potential therapeutic compounds. Results L1000 fireworks display (L1000FWD) is a web application that provides interactive visualization of over 16 000 drug and small-molecule induced gene expression signatures. L1000FWD enables coloring of signatures by different attributes such as cell type, time point, concentration, as well as drug attributes such as MOA and clinical phase. Signature similarity search is implemented to enable the search for mimicking or opposing signatures given as input of up and down gene sets. Each point on the L1000FWD interactive map is linked to a signature landing page, which provides multifaceted knowledge from various sources about the signature and the drug. Notably such information includes most frequent diagnoses, co-prescribed drugs and age distribution of prescriptions as extracted from the Mount Sinai Health System electronic medical records. Overall, L1000FWD serves as a platform for identifying functions for novel small molecules using unsupervised clustering, as well as for exploring drug MOA. Availability and implementation L1000FWD is freely accessible at: http://amp.pharm.mssm.edu/L1000FWD. Supplementary informationSupplementary dataare available at Bioinformatics online.