The basic unit of chromatin is double-stranded DNA wrapped around nucleosome core particles, the �classic “beads-on-a-string” described by Kornberg and colleagues. The history of chromatin studies has experienced many peaks, from the earliest studies by Miescher to the biochemical studies of the 1960s and 1970s, the appreciation for the influence of histone modifications in controlling gene expression in the 1990s to the genome-wide studies that began in 2006 and show no signs of abating with the introduction of next generation sequencing technologies. Genome-wide studies not only have provided a base line to understand relationships between chromatin structure and gene function but also have begun to provide new insights into chromatin remodelling. Here, we describe the use of genome-wide approaches to determining nucleosome occupancy in yeast.