T cells respond to threats in an antigen-specific manner using T cell receptors (TCRs) that recognize short peptide antigens presented on major histocompatibility complex (MHC) proteins. The TCR–peptide-MHC interaction mediated between a T cell and its target cell dictates its function and thereby influences its role in disease. A lack of approaches for antigen discovery has limited the fundamental understanding of the antigenic landscape of the overall T cell response. Recent advances in high-throughput sequencing, mass cytometry, microfluidics and computational biology have led to a surge in approaches to address the challenge of T cell antigen discovery. Here, we summarize the scope of this challenge, discuss in depth the recent exciting work and highlight the outstanding questions and remaining technical hurdles in this field.