Transgenic engineering of plants is important in both basic and applied research. The process of generating elite transgenic events in many crops is arduous and from the large population of transgenic events produced in the initial tissue culture stage, only a small subpopulation give high levels of transgene performance that are stable in subsequent generations. It has been suggested that high transgene expression triggers silencing pathways and that initial highly expressing events soon become incapacitated. To overcome this drawback, we need to better understand how a plant recognises the difference between its own genes (self) and transgenes (non-self). Our recent work, using a mutant screen in Arabidopsis, has identified five genes affecting the plant’s perception of self. Insights into how a plant perceives self vs non-self-genes will be discussed.