Embryos, oocytes and spermatozoa undergo several manipulations during the in vitro procedures that are an integral part of assisted reproductive technologies (ART) in mammals. Consequently, some of the gametes are damaged irreparably, whereas others react to these challenges with some sort of survival mechanism that enables them to come through the process. The details of the mechanism remain unknown but, if identified, it could have immense potential as a new way to improve the viability of embryos produced by ART. However, few publications describe systematic ways to challenge test gametes and then to use the results as a basis for improving gamete viability. Furthermore, new methods to monitor the reactions of gametes to such challenge tests are needed. In the present review, these two issues are discussed, as are some of the conditions necessary before a challenge test protocol can be part of future work with ART.