The problem of designing new keyboards layouts able to improve the typing speed of an average message has been widely considered in the literature of the Ergonomics domain. Empirical tests with users and simple optimization criteria have been used to propose new solutions. On the contrary, very few papers in Operations Research have addressed this optimization problem. In this paper we firstly resume the most relevant problems in keyboard design, enlightening the related Ergonomics aspects. Then we concentrate on keyboards that must be used witha single finger or stylus, like that of Portable Data Assistant, Smartphones and other small devices.We show that the underlying optimization problem is a generalization of the well known Quadratic Assignment Problem (QAP). We recall some of the most effective metaheuristic algorithms for QAP and we propose some non trivial extensions to the keyboard design problem. We compare the new algorithms through computational experiments with instances obtained from word lists of the English, French, Italian and Spanish languages. We provide on the web benchmark instances for each language and the best solutions we obtained.