Dictyostelium has a good potential to serve as a model for the study of chromatin function and epigenetic gene regulation. The organism bridges the complexity of higher eukaryotic systems and the simplicity of yeast in that it harbors pathways that are similar to the former and is accessible to genetic manipulation like the latter. The findings that, in contrast to previous assumptions, Dictyostelium DNA contains methylated cytosine and that the RNA interference machinery may be involved in chromatin remodeling, open up new avenues to investigate epigenetic aspects in one of the most simple developing organisms. The protocols in this chapter describe the more recent techniques established for other organisms, with an emphasis on special precautions for application in Dictyostelium.