The use of reclaimed water in crop irrigation helps to mitigate water shortage. The fertilization of arable soils with sewage sludge, biosolids, or livestock manure reduces extensive application of synthetic fertilizers. However, both practices lead to the introduction of pharmaceutical active compounds (PhACs) in arable soil, known to host a wide range of living organisms, including microorganisms which are supporting numerous ecosystem services. In soils, the fate of PhACs is governed by different abiotic and biotic processes. Among them, soil sorption and microbial transformation are the most important ones and determine the fate, occurrence, and dispersion of PhACs into the different compartments of the environment. The presence of PhACs in soils can compromise the abundance, diversity, and activity of the soil microbial community which is one of the key players in a range of soil ecosystem services. This chapter reviews the current knowledge of the effects of PhACs, commonly found in wastewater effluents and derived organic fertilizers, on the soil microbial community.