To set conservation priorities, scientists should be able to assess the relative threats posed by the effects of loss of genetic variability, inbreeding and outbreeding as these can generate 'genetic stress'. Developmental instability (DI) has been suggested as an indicator of stress, possibly being more sensitive than other measures. However, there is controversy as to whether DI is an accurate and reliable tool for assessing the degree of genetic stress. After 50 years of the presentation of Lerner's conjecture, there are still several unresolved questions about the relationship between DI and genetic stress. Here, we review studies on mechanisms behind DI. The current status on the use of DI as an indicator of genetic stress is discussed, and suggestions are presented on how to obtain more knowledge on the potential of DI in an evolutionary context.