In a horizontal subsurface flow constructed wetland (HFCW) the passage of wastewater through the package media allows the contact and interaction between their biotic (bacteria and vegetation) and abiotic components (wastewater and package media), resulting in synergy for pollutant removal. Indeed, the efficacy of these treatment systems for recalcitrant and toxic compounds and pollutants removal has been demonstrated for more than two decades. This chapter aims to exhibit the HFCW application trends to immobilize, remove, stabilize, and degrade toxic pollutants such as pharmaceutical compounds, dyes, metals, pesticides, and those present in combined drainage. Besides, an overview of recent developments for toxic substance removal is shown. Therefore, this chapter provides basic and general information about the main removal mechanisms occurring in HFCW for those toxic pollutants elimination. Finally, a future technical perspective in this field of constructed wetlands is given.