It is increasingly appreciated that the mechanical properties of the microenvironment around cells exerts a significant influence on cell behavior, but careful consideration of what is the physiologically relevant elasticity for specific cell types is required to produce results that meaningfully recapitulate in vivo development. Here we outline methodologies for excising and characterizing the effective microelasticity of tissues; but first we describe and validate an atomic force microscopy (AFM) method as applied to two comparatively simple hydrogel systems. With tissues and gels sufficiently understood, the latter can be appropriately tuned to mimic the desired tissue microenvironment for a given cell type. The approach is briefly illustrated with lineage commitment of stem cells due to matrix elasticity.