Rapid activation of immune cells is critical for host defence. While transcriptional regulation is essential for initiating the immune response, emerging evidence highlights the role of post-transcriptional mechanisms in controlling the speed and intensity of the immune reaction. Splicing, polyadenylation, translation and decay are all regulated to fine-tune the expression of genes crucial for immune cell activation and differentiation. Therefore, it is not surprising that impaired mRNA regulation results in susceptibility to infection, inflammation or immune deficiency. An in-depth understanding of these processes is critical for developing novel therapies for immune diseases. This Review provides an integrative view of how mRNA splicing, polyadenylation and decay control immune cell activation and effector function.