The beneficial effects of alpha-hydroxyacids (AHAs) on skin were discovered by Drs. Van Scott and Yu in the early 1970s, including exfoliation, skin smoothing, and antiaging effects. A new generation of AHAs, called polyhydroxy acids (PHAs), was discovered that provide similar effects as AHAs but do not cause the sensory irritation responses that can limit the use of classical AHAs. PHAs have been found to be compatible with clinically sensitive skin, including rosacea and atopic dermatitis, and can be used after cosmetic procedures. PHAs provide additional humectant and moisturization properties compared with AHAs and can enhance stratum corneum barrier function, therefore increasing the skin's resistance to chemical challenge. Most PHAs also possess antioxidant properties. PHAs such as gluconolactone or lactobionic acid may be used in combination with other products, ingredients, or procedures such as laser and microdermabrasion to provide additional benefits to therapy or to enhance the therapeutic effect. Several studies were conducted in support of this, and methods and results are discussed. In summary, PHA-containing products were used in combination with retinoic acid in treating adult facial acne and were found to be well tolerated. PHAs plus retinyl acetate (pro-vitamin A) in a cream base exhibited significant antiaging skin benefits such as skin smoothing and plumping. PHAs plus hydroquinone showed excellent improvement in antiaging and skin lightening parameters. Finally, PHA-containing products were shown to be compatible with African American, Caucasian, and Hispanic/Asian skin and provided significant improvements in photoaging in these populations.