Both instrumentation and computational methodologies play a major role in the study of cells and the immune system. In this chapter, we discuss the basic principles of next generation sequencing (NGS) technology, highlighting the applications of NGS in the understanding of the immune system. Computational modeling and analysis can help in the analysis of high throughput data generated by NGS. Understanding the functions of a single cell has greatly developed in the recent past with the tools and techniques in single cell transcriptomics (SCT). This has enabled us to study the behavior of each cell in the milieu of other cells. In the immune system, the activity of antigen-specific T and B cells can be understood by techniques encompassing transcriptomics, proteomics, and imaging approaches. In this chapter, we discuss the different techniques involved in single cell transcriptomics, highlighting the application of computational tools in understanding immune cell biology, cell differentiation, and cancer.