Hydrogels are polymer networks infiltrated with water, widely used for tissue engineering vehicles of drug delivery and novel platforms for biomedical engineering. Emerging applications for new hydrogel materials call for robustness under cyclic mechanical loads. Materials scientists have developed tough hydrogels that resist fracture under a single cycle of mechanical load, yet these toughened gels still suffer from fatigue fracture under multiple cycles of loads. The present fatigue threshold for synthetic hydrogels is reported in the order of 1 to 100 J/m2.