Consumption of untreated or partially treated water can result in gastrointestinal infections caused by pathogenic microorganisms. Point-of-use (POU) water treatment, where water is treated in the home just before consumption, can at least partially address this problem in areas of the world that lack appropriate drinking water treatment and/or distribution infrastructure. In general, current technologies provide a low-cost solution to combat microbial pathogens and improve water quality. But they face technological or handling issues impacting their performance. The physicochemical quality of the water to be treated, the presence of inorganic and organic reduced compounds, and the aggregation of pathogens play important roles in the disinfection effectiveness of the chemical disinfectants used in POU technologies (e.g., silver and free chlorine). The use of combinations of these disinfectants in doses that meet the World Health Organization guidelines for drinking water, have resulted in synergistic inactivation of bacterial species. And alternative technologies that include insoluble N-chloramines are also promising as effective water disinfectants since these polymers can provide very high effective chlorine (+1) ion concentrations. This chapter shows current knowledge of copper and silver ions, free chlorine, and N-chloramines in POU drinking water treatment applications, including kinetics and mechanisms of inactivation of pathogens, toxicity, and synergistic effects produced by combinations of these chemical disinfectants. With this, we aim to present the potential to improve POU technologies to increase the efficacy of inactivation of waterborne pathogens while avoiding or reducing the formation of disinfection byproducts and disinfectant residuals toxicity.