The integrin β1 subfamily of adhesion receptors consists of 12 members and forms the biggest subfamily among integrins. Human integrin subunit beta1 has five cytoplasmic splice variants (β1A, β1B, β1C-1, β1-C2, β1D). Even though cytoplasmic splice variants do not change the ligand-specificity of a β1 integrin, clustering of these different splice variants triggers signaling pathways that lead to a different cellular response. The main focus of this review is on the origin and specific functions of the less abundant human integrin β1 splice variants (B, C-1, C-2, D).