The genetic consequences of inbreeding is a subject that has received thorough theoretical attention and has been of interest to empirical biologists since the time of Darwin. Particularly for species with genetically controlled mechanisms to promote outcrossing (self-incompatibility or SI systems), it is expected that high levels of genetic load should accumulate through sheltering of deleterious recessive mutations. Nevertheless, transitions to selfing are common across angiosperms, which suggests that the potentially negative consequences of reduced heterozygosity and genetic diversity are balanced by other factors, such as reproductive assurance. This mini-review focuses on empirical research in the Brassicaceae to emphasize some of the genetic consequences of shifts to inbreeding in terms of mechanisms for loss of SI, changes in genetic diversity following loss of SI, and inbreeding depression in relation to outcrossing history. Despite the long history of theoretical attention, there are still some surprisingly large gaps in our understanding in each of these areas. Rather than providing a complete overview, examples are drawn predominantly from published and emerging data from Arabidopsis thaliana and its relatives to highlight recent progress and remaining questions. We are currently on the brink of major breakthroughs in understanding due both to advances in sequencing technology and a shift in focus from crop plants to natural populations, where critical factors such as population structure, phylogeography, demographic history, partial compatibility and individual variation can be taken into account when investigating the nature of the selective forces regulating mating system evolution.