Aquagenic wrinkling of the palms (AWP) is a rare, acquired condition of the skin, defined by transient rapidly developing white to translucent papules on palms and/or soles after brief exposure to water. Aquagenic wrinkling of the palms is associated with cystic fibrosis (CF). Therefore, the diagnosis of AWP can be important. Etiopathogenesis of AWP is still unclear. Treatment is often unsatisfactory and can be very challenging. This article contributes to the knowledge of AWP as we describe two new cases of aquagenic wrinkling of the palms: one patient with familial history of CF and one patient with AWP that was presumed to be induced by use of non-steroidal anti-inflammatory drugs. In addition, we present a review of the literature on drug-induced AWP.