The approval of chemicals for placing on the market is subject to various regulations in many countries. Regulations often require the assessment of the environmental fate in simulation tests using isotope labels for facilitated analysis. Such tests simulate the turnover of a chemical in complex environmental systems such as soils, water-sediment or wastewater treatment systems. Non-extractable residues (NER) are formed during the turnover of organic chemicals in solid matrices. NER are the ‘black box’ in current risk assessments of organic chemicals since their chemical composition is largely unknown. NER can result from sorption of the parent compound or its primary transformation products to the solid matrix; this leads to xenobiotic NER formation (considered as ‘hidden hazard’). However, microbial biomass formed during microbial biodegradation of chemicals can also contribute substantially to NER formation (biogenic NER; considered as ‘safe sink’ of no environmental concern). Biogenic NER thus need to be distinguished from the toxic xenobiotic NER in improved risk assessments and registration procedures of chemicals. The formation and the analytics of NER have so far only been phenomenologically described. This chapter describes the general microbial degradation processes of organic chemicals and summarizes the state of the art on NER analytics with particular focus on biogenic NER. Knowledge gaps in the NER analytics and suggestions for improvement are presented.