The process of de novo gene birth involves the evolution of genes from non-genic DNA sequences. While there are numerous ideas that outline potential pathways of the genesis of new genes, the governing processes remain poorly understood. De novo gene birth can happen at any time during an organism`s evolutionary history; however, it is challenging to identify early de novo events. Most studies of de novo genes focus on genes found in a single species or lineage, which are usually taxonomically restricted. This article discusses genomic phylostratigraphy, synteny-based approaches to de novo emerging sequences in the genome, as well as prevalence, dynamics, and status of gene birth. It is noteworthy that genes arise de novo through well-characterized mechanisms such as overprinting, exonization, random sequence evolution and male-biased expression. In other words, instead of being inactive and silent, non-genic regions may store potential genes in a dynamic manner.