Integrins are heterodimeric complex type I membrane proteins involved in cellular adhesion and signaling. They exist as inactive molecules in resting cells, and need activation to become adhesive. Although much is known about their structure, and a large number of interacting molecules have been described, we still only partially understand how their activities are regulated. In this review we focus on the leukocyte-specific β2-integrins and, specifically, on the role of integrin phosphorylation in the regulation of activity. Phosphorylation reactions can be fast and reversible, thus enabling strictly directed regulatory activities both time-wise and locally in specific regions of the plasma membrane in different leukocytes.