There is a remarkable diversity of sex chromosome systems among closely related Poecillids. Importantly, Poecilia picta is the first example of complete sex chromosome dosage compensation in fishes. Thus, these species are an ideal system to study sex chromosome divergence and the evolution of dosage compensation as it relates to sex differences. However, the use of P. picta is hindered by the lack of a well assembled and annotated genome. The opportunity to examine sex differences in the genome and epigenome of P. picta will allow us to significantly advance our understanding of how sex chromosomes and dosage compensation systems evolve, and the role of epigenetic mechanisms in sex chromosome dosage compensation. A reference genome will also significantly aid in studies of ecological adaptation and evolution.