Mass spectrometry is versatile and ideally suited for the study of infectious disease. I will present data that demonstrates how a combination of traditional discovery based proteomics and targeted analyses allow a systematic study of viral infection and the immune response both in vitro and in vivo. This will include the identification of novel T cell epitopes, quantitation of these epitopes on the surface of infected cells, correlation of viral antigen expression with epitope liberation and the T cell response. The combination of deep sequencing using LC-MS/MS, targeted multiple reaction monitoring and data independent acquisition SWATH-MS illustrates the power of mass spectrometry in the study of complex biological systems.