The extracellular matrix is a crucial component in determining cell fate. Fibrillar collagen, in its native form inhibits cell proliferation, whereas in its monomeric form it stimulates proliferation. The observation of elevated levels of p27KIP1 in cells grown in the presence of fibrillar collagen has led to the assumption that this kinase inhibitor was responsible for the cell cycle arrest on fibrillar collagen. Here we provide evidence that p15INK4b, rather than p27KIP1, is the cyclin dependent kinase inhibitor responsible for G0/G1 arrest of human melanoma cells grown on fibrillar collagen. Additionally, we demonstrate that fibrillar collagen arrests cells at the G2 phase which is mediated in part by p21CIP1. Our data, in addition to identifying cyclin dependent kinase inhibitors important in cell cycle arrest mediated by fibrillar collagen, demonstrates the complexity of cell cycle regulation and indicates that modulating a single cyclin dependent kinase inhibitor does not disrupt cell proliferation in the presence of fibrillar collagen.