Single-cell nanoencapsulation is an emerging field in cell-surface engineering, emphasizing the protection of living cells against external harmful stresses in vitro and in vivo. Inspired by the cryptobiotic state found in nature, cell-in-shell structures are formed, which are called artificial spores and which show suppression or retardation in cell growth and division and enhanced cell survival under harsh conditions. The property requirements of the shells suggested for realization of artificial spores, such as durability, permselectivity, degradability, and functionalizability, are demonstrated with various cytocompatible materials and processes. The first-generation shells in single-cell nanoencapsulation are passive in the operation mode, and do not biochemically regulate the cellular metabolism or activities. Recent advances indicate that the field has shifted further toward the formation of active shells. Such shells are intimately involved in the regulation and manipulation of biological processes. Not only endowing the cells with new properties that they do not possess in their native forms, active shells also regulate cellular metabolism and/or rewire biological pathways. Recent developments in shell formation for microbial and mammalian cells are discussed and an outlook on the field is given.