The major growth seen in the biotechnology industry in recent decades has largely been driven by the exploitation of genetic engineering techniques. The initial benefits have been predominantly in the biomedical area, with products such as vaccines and hormones that have received broad public approval. In the environmental biotechnology and industrial ecology sectors, biotechnology has the potential to make significant advances through the use of genetically modified (GM) microbial inoculants that can reduce agri-chemical usage or remediate polluted environments. Although many GM inoculants have been developed and tested under laboratory conditions, commercial exploitation has lagged behind. Here, we review scientific and regulatory requirements that must be satisfied as part of that exploitation process. Particular attention is paid to new European Union (EU) regulations (Directives) that govern the testing and release of genetically modified organisms and microbial plant protection inoculants in the EU. With regard to the release of GM inoculants, the impact of the inoculant and the fate of modified genes are important concerns. Long term monitoring of release sites is necessary to address these issues. Data are reported from the monitoring of a site 6 years after release of GM Sinorhizobium meliloti strains. It was found that despite the absence of a host plant, the GM strains persisted in the soil for at least 6 years. Horizontal transfer and microevolution of a GM plasmid between S. meliloti strains was also observed. These data illustrate the importance of assessing the long-term persistence of GM inoculants.