Fundamental aspects of the interactions between cells and biomaterials provide a crucial framework for the design of many systems that interact with the human body. A comprehensive understanding of multifactorial processes may provide an adequate basis for the rational design of implantable devices ranging from nanoparticles for drug delivery and scaffolds for tissue engineering, to artificial organs for augmentation and rehabilitation. Recent progress in the elucidation of cell-biomaterials interactions has been predicated on advances in polymer chemistry, materials engineering, and device microfabrication. The confluence of these developments has stimulated a newfound ability to design soft materials and interfaces with precise chemical, physical, and mechanical properties. While static surfaces can yield insight into the interaction of mammalian cells with medical materials, the study of fundamental cell-biomaterials phenomena will benefit significantly from the ability to present biologically active signals to cells with spatiotemporal control. Specifically, the use of dynamic materials and interfaces can mirror the intrinsic dynamic behavior of living cells. This article highlights recent advances in soft materials design, interfacial engineering, and synthetic polymer networks in the context of producing dynamic materials to study cell-biomaterials interactions. Emerging challenges and future research directions are also discussed.