Synthetic and natural polymers are an important element in new strategies for producing engineered tissue. Polymers are currently used in a wide range of biomedical applications, including applications in which the polymer remains in intimate contact with cells and tissues for prolonged periods. As discussed in Chapter 1, several classes of polymers have proven to be most useful in biomedical applications and, therefore, might be appropriate for tissue engineering applications. To produce tissue-engineered materials composed of polymers and cells, however, it is first necessary to understand the influence of these polymeric materials on cell viability, growth, and function. Cell interactions with polymers are usually studied using cell culture techniques. While in vitro studies do not reproduce the wide range of cellular responses observed following implantation of materials, the culture environment provides a level of control and quantification that cannot usually be obtained in vivo. Cells in culture are generally plated over a polymer surface and the extent of cell adhesion and spreading on the surface can be measured. By maintaining the culture for longer periods the influence of the substrate on cell viability, function, and motility can also be determined. Since investigators use different techniques to assess cell interactions with polymers, and because the differences between techniques are critically important for interpretation of interactions, some of the most frequently used in vitro methods are reviewed in this section. Before any measurement of cell interaction with a polymer substrate can be attempted, the polymeric material and the cells must come into contact. Preferably, this contact should be controlled (or at least understood) by the experimentalist. This is a critical, and often overlooked, aspect of all of these measurements. Some materials are easily fabricated in a format suitable for study; polystyrene films, for example, are transparent, durable, and strong. Other materials must be coated onto a rigid substrate (such as a glass coverslip) prior to study. Cell function is sensitive to chemical, morphological, and mechanical properties of the surface; therefore, almost every aspect of material preparation can introduce variables that are known to influence cell interactions.