The article reviews the role of intercellular adhesion molecules (ICAMs) in immune responses, focusing on their interactions with β2 integrins and their significance in various cellular processes. ICAMs, including ICAM-1, -2, and -3, are crucial for leukocyte activation, differentiation, and migration. They bind to β2 integrins, which are key mediators of homotypic and heterotypic leukocyte adhesion. The review highlights the importance of ICAMs in signal transduction, particularly in T-cell activation, differentiation, and migration. ICAMs are also involved in the regulation of the actin cytoskeleton, which affects cell adhesion and migration. Additionally, ICAMs play a role in disease states such as dry eye disease, cardiovascular disease, intestinal inflammation, pulmonary fibrosis, autoimmunity, hematopoietic stem cell transplantation, and cancer. The article discusses the potential of ICAMs as biomarkers and therapeutic targets in these conditions.The article reviews the role of intercellular adhesion molecules (ICAMs) in immune responses, focusing on their interactions with β2 integrins and their significance in various cellular processes. ICAMs, including ICAM-1, -2, and -3, are crucial for leukocyte activation, differentiation, and migration. They bind to β2 integrins, which are key mediators of homotypic and heterotypic leukocyte adhesion. The review highlights the importance of ICAMs in signal transduction, particularly in T-cell activation, differentiation, and migration. ICAMs are also involved in the regulation of the actin cytoskeleton, which affects cell adhesion and migration. Additionally, ICAMs play a role in disease states such as dry eye disease, cardiovascular disease, intestinal inflammation, pulmonary fibrosis, autoimmunity, hematopoietic stem cell transplantation, and cancer. The article discusses the potential of ICAMs as biomarkers and therapeutic targets in these conditions.