The pharmaceutical occurrence in surface and ground water bodies is due to low efficiency of the wastewater treatment plants in removing those pollutants. Their biological transformation using white-rot fungi has been proposed due to their unspecific intracellular and extracellular oxidoreductase enzymatic systems. This chapter summarizes and analyzes the studies performed on pharmaceuticals removal from urban and hospital wastewater using fungal reactors operating in batch or continuous mode. Due to low fungal growth rate, all reactors are based on the biomass reuse through the retention through the pellet morphology or membrane, or by immobilization on a support. The treatment of real wastewater in non-sterile conditions requires the assessment of effect of the native microorganism on the fungal treatment. The chapter also offers an insight into fungal enzymatic systems, types of reactors, and strategies to reduce bacteria effect and consequently maintaining fungal activity during a continuous treatment during long periods.