This review examines the systemic insecticides neonicotinoids and fipronil, focusing on their trends, uses, mode of action, and metabolites. Neonicotinoids, discovered in the late 1980s, have become the most widely used class of insecticides globally, with applications ranging from plant protection to veterinary products and invertebrate pest control in fish farming. Fipronil, a phenyl-pyrazole compound, is also reviewed due to its similarities in toxicity and physicochemical properties to neonicotinoids. The initial success of neonicotinoids and fipronil was attributed to their lack of known resistance in target pests, superior physicochemical properties compared to previous insecticides, and perceived reduced risks to operators and consumers. Their systemic nature allows them to be taken up by plant roots or leaves and translocated throughout the plant, making them effective against herbivorous insects. However, their extensive use and persistence in the environment have raised concerns about potential risks to non-target organisms and ecosystems. Neonicotinoids disrupt neural transmission in the central nervous systems of invertebrates by mimicking neurotransmitters, while fipronil inhibits neuronal receptors, leading to continuous neuron stimulation and ultimately death. These compounds can have lethal and sublethal impacts on non-target organisms, including insect predators and vertebrates, and synergistic effects with other stressors have been documented. The review also discusses the metabolic pathways of these compounds, showing how they form compound-specific and common metabolites that can be toxic. The persistence and environmental fate of neonicotinoids and fipronil, along with limited information about their toxicity profiles, highlight the need for a global evaluation of their potential environmental impacts. The paper and subsequent chapters in this review explore these risks and provide evidence of serious environmental concerns associated with persistent, low concentrations of these insecticides.This review examines the systemic insecticides neonicotinoids and fipronil, focusing on their trends, uses, mode of action, and metabolites. Neonicotinoids, discovered in the late 1980s, have become the most widely used class of insecticides globally, with applications ranging from plant protection to veterinary products and invertebrate pest control in fish farming. Fipronil, a phenyl-pyrazole compound, is also reviewed due to its similarities in toxicity and physicochemical properties to neonicotinoids. The initial success of neonicotinoids and fipronil was attributed to their lack of known resistance in target pests, superior physicochemical properties compared to previous insecticides, and perceived reduced risks to operators and consumers. Their systemic nature allows them to be taken up by plant roots or leaves and translocated throughout the plant, making them effective against herbivorous insects. However, their extensive use and persistence in the environment have raised concerns about potential risks to non-target organisms and ecosystems. Neonicotinoids disrupt neural transmission in the central nervous systems of invertebrates by mimicking neurotransmitters, while fipronil inhibits neuronal receptors, leading to continuous neuron stimulation and ultimately death. These compounds can have lethal and sublethal impacts on non-target organisms, including insect predators and vertebrates, and synergistic effects with other stressors have been documented. The review also discusses the metabolic pathways of these compounds, showing how they form compound-specific and common metabolites that can be toxic. The persistence and environmental fate of neonicotinoids and fipronil, along with limited information about their toxicity profiles, highlight the need for a global evaluation of their potential environmental impacts. The paper and subsequent chapters in this review explore these risks and provide evidence of serious environmental concerns associated with persistent, low concentrations of these insecticides.