Tools for editing the genome and epigenome represent a new frontier in targeted therapeutic intervention. Nonviral nanoparticle-based delivery systems are potentially the long-term future for delivering gene therapies in vivo in a safe and controllable manner. Currently, nonviral agents fail to couple delivery efficiency across cell type with low toxicity and the ability to deliver large or multiple payloads, rendering clinical implementation of these technologies elusive. Herein we review recent developments in the evaluation of polymeric and inorganic nanoparticles as nonviral methods to deliver current genome editing tools. In particular, this chapter will focus on in vivo delivery of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and the CRISPR-associated protein 9 (Cas9), and the current bottlenecks the field faces.