We present our achievements in the synthesis and application of multifunctionalized, cross-linked, polystyrene microspheres, which remarkably and quite generally are taken up by all cell types studied to date. Importantly, the nature of these synthetic beads allows multistep solid-phase chemistry and the ability to bind essentially any molecule/sensor/nucleic acid to them. These microspheres have a number of advantages over other cellular delivery approaches. First, a diverse range of compounds can be attached to the microspheres, and we have demonstrated that these materials are effectively delivered into cells; second, the cellular cargo can be modulated through modification of bead loading; third, they are large enough to be visualized using standard microscopy techniques; and fourth, their cargos are not diluted within the cell. Populations of cells containing beads can be readily sorted from other cells for subsequent analysis with very high, but controllable, uptake rates, which can be modulated through modulation of the bead size and incubation time. Recent work has focused on the development of these microspheres as sensors for intracellular calcium and pH.