Recently developed sequencing technologies have increased both the sensitivity and depth at which large number of T cell and B cell receptors can be identified and quantitated from different biological tissues. High-throughput sequencing of B cell and T cell receptors (immunosequencing) makes it possible to not only identify target-specific receptors, but to accurately track the frequencies of individual T and B cell clonotypes over time. Immunosequencing is being used to better understand antigen specificity of adaptive immune responses to infectious agents and autoimmunity, to identify new tumor antigens, and to monitor responses to immunotherapies. In this review we will discuss the current uses and potential future applications of immunosequencing.