Vascular smooth muscle cell (VSMC) modulation to a de-differentiated phenotype and proliferation are key components of vascular lesion formation. Understanding how these processes are regulated is essential to understanding the progression of vascular diseases such as atherosclerosis and in-stent restenosis. The Id family of helix-loop-helix (HLH) transcription factors has emerged as important regulators of cellular growth and differentiation. Recent published findings have implicated the Id proteins as important regulators of growth and phenotypic modulation in VSMC and in the vascular response to injury. In this review, we summarize what is known regarding how the Id proteins function to control cellular growth and differentiation and their role in vascular lesion formation.