Linearly elastic elastomers coated with matrix proteins are widely used to assess the role of stiffness. Such experiments are often assumed to reproduce the effect of the mechanical environment experienced by cells in vivo. However, tissues and the extracellular matrix (ECM) are not linearly elastic materials. They exhibit far more complex mechanical behaviors. These behaviors include viscoelasticity, as well as mechanical plasticity, and nonlinear elasticity. Our theoretical and experimental work has revealed that matrix viscoelasticity regulates fundamental cell processes and can promote behaviors – such as proliferation, motility and spreading – that are not observed with elastic hydrogels in both two- and three-dimensional culture microenvironments.