In this chapter, practical experimental issues associated with the mechanical testing of biological materials are considered. Nanoindenters and atomic force microscope devices are considered in separate sections, with best practice recommendations for testing materials of different stiffnesses in each configuration. Technical aspects of commercial instrumentation are examined, including load and displacement resolution, load and displacement ranges, stability of the instrument signals and compliance of the load-frame. Significant emphasis is placed on mechanisms for achieving environmental control necessary for biological materials testing, including temperature and humidity effects, specimen preparation and stability of the biological samples themselves.