The precise signals responsible for differentiation of circulating monocytes into tissue macrophages are incompletely defined. "Outside-in" integrin signaling has been implicated in modulating gene expression that affects cellular differentiation. This review highlights the role of transcription factors in monocyte differentiation and describes how integrin engagement orchestrates monocyte differentiation signals by regulating the expression of the forkhead transcription factor Foxp1, which functions as a transcriptional repressor of the macrophage colony-stimulating factor receptor c-fms. This represents a new pathway for integrin-dependent modulation of gene expression and control of cellular differentiation.