A Proliferation Inducing Ligand (APRIL) was first identified as a cytokine expressed predominantly by tumour tissues and was not found in most normal tissues. The activity of this new cytokine, in terms of its ability to stimulate tumour cell proliferation in vivo, determined the catchy acronym of yet another TNF family cytokine: APRIL. Reports showing an association between APRIL and cancer have since been prolific, in particular, those showing a link with B cell malignancies. Evidence is accumulating that APRIL is also a player in several autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, and Sjoegren's syndrome. However, we now know that APRIL also plays an important role in the immune system and in lymphocyte biology. In this chapter we outline the physiological role of APRIL in immunity and describe what is known regarding the role of APRIL in B cell malignancies and autoimmune disease.