High-performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD) is a well-established technique for carbohydrate determinations. This chapter first reviews the basics of HPAEC-PAD and new developments in column and electrochemical detection technologies. The remainder of the chapter is dedicated to the application of HPAEC-PAD. The major applications of HPAEC-PAD: monosaccharide analysis, sialic acid analysis, and glycan/oligosaccharide profiling are updated. Then applications that have either increased in popularity or emerged in the last 20 years are described: profiling human milk oligosaccharides, analyzing glycoconjugate vaccines, carbohydrate determinations in biofuel research, determination of carbohydrates in urine and serum, determination of carbohydrates in atmospheric aerosols, and determination of carbohydrates in plants and food. The chapter concludes showing the role of HPAEC-PAD in regulatory and standard methods.