Since the mid-1970s, genetic engineering and the possibility of accidental or deliberate environmental release of modified micro-organisms has been the centre of debates concerning the consequences of altering the ordinary course of nature. For a sound discussion on risks, it is of essence to separate substantive scientific and technical issues from non-informed perceptions of the general public. This chapter advocates this question to be framed on the already extensive history and wealth of data on the design, performance and risk studies made since the early 1980s on genetically modified organisms and more specifically, on available records on genetically engineered micro-organisms (GEMs) designed for non-contained applications as in situ bioremediation agents. Existing information provides a suitable background for tackling the uncertainties raised by newly engineered agents, including those that may stem from synthetic biology.