EUROSTAT figures show that 5720 people die in the European Union every year as a consequence of work-related accidents. Training in Health and Safety is indeed a key aspect to reduce this figure, and serious games constitute an effective method to provide this training. However, the development of this type of computer applications is a complex issue, requiring cross discipline knowledge on different areas, including instructional design, psychology, sociology, law, and computer graphics. Beyond the challenges already present in the development of non-educational computer games, serious games for health and safety are instructional tools. Therefore, they require an instructional design to cover specific educational issues, and knowledge on the health and safety regulations which are applicable in each particular context. In addition, these games have as their ultimate goal to increase the worker’s awareness about safety regulations and reduce the number and seriousness of accidents. Thus, the evaluation of this type of applications must be rather different from the evaluation of other games with a focus on entertainment. In this chapter we provide a description of existing serious games in the health and safety area, and describe major instructional and technological aspects related to the development of this type of training tools. Although technological developments will indeed increase the advantages of serious games as a means to deliver instruction in health and safety, we believe that the most challenging issues remain at the instructional side, and further research is still needed to maximize the effectiveness of this kind of training.