Cell-encapsulating hydrogels are of tremendous interest in regenerative medicine. Tissue engineering relies on biomaterials able to act as artificial extracellular matrices to guide cells towards the development of new tissues. Therefore, considerable efforts have been made to design biomaterials which mimic cells’ native environment, thus encouraging natural behavior. The choice of biomaterial in which cells are embedded is crucial for their survival, proliferation and differentiation. Being more stable, chemical hydrogels are preferred over physical hydrogels as cell-laden substrates. When designing chemical hydrogels, scientists must choose not only the nature of the network (synthetic and/or bio-polymers) but also the type of cross-link bridging hydrogel constituents. For that purpose, numerous chemistries have been used (i) to introduce reactive functions on the hydrogel precursors and (ii) to form covalent bonds in the presence of living cells. The review will discuss the advantages and limitations of each strategy.