Tumor necrosis factor alpha (TNFα) is a pro-inflammatory cytokine that triggers the expression of inflammatory molecules, including other cytokines and cell adhesion molecules. TNFα induces the expression of intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1 (VCAM-1). VCAM-1 was originally identified as a cell adhesion molecule that helps regulate inflammation-associated vascular adhesion and the transendothelial migration of leukocytes, such as macrophages and T cells. Recent evidence suggests that VCAM-1 is closely associated with the progression of various immunological disorders, including rheumatoid arthritis, asthma, transplant rejection, and cancer. This review covers the role and relevance of VCAM-1 in inflammation, and also highlights the emerging potential of VCAM-1 as a novel therapeutic target in immunological disorders and cancer.