Palmoplantar pustulosis (PPP) is difficult to treat. There is little hard evidence for the efficacy of any treatment and no published guidelines for its management. A number of exacerbating factors are well documented and there is some evidence for the importance of others. Smoking is the most recognized environmental trigger and recent research has concentrated on the role of eccrine sweat glands in this regard. Other factors, including tonsillar streptococcal infection and gluten sensitivity, may be important in selected cases. The aim of this review is to challenge dermatologists to consider alternative management strategies for PPP and design clinical trials that will enable the development of useful therapeutic guidelines.