Enhancers are cis-regulatory elements that spatiotemporally modulate gene expression. However, our understanding of how enhancers activity is encoded in the genome is incomplete. Unlike protein-coding genes, the evolutionary conservation of enhancers appears the exception rather than the rule, even between mammals. A comprehensive mechanistic knowledge of the sequences required for context-specific enhancer activity is unknown for most, if not all, cell states and cell types. I will discuss our work to interrogate enhancer evolution through changes associated with DNA replication timing as well as our current work using high-throughput molecular methods and deep learning to understand the sequence basis of cell-type specific enhancer activity.