The adoption of microfluidics was fundamental to the development of cost-effective, high-throughput DNA sequencing. As the field progresses towards multi-omics, we reflect on the key concepts underlying microfluidics and how resulting engineering advances at the microscale drove the evolution of genomic sequencing. The adoption of microfluidics was fundamental to the development of cost-effective, high-throughput DNA sequencing. As the field progresses towards multi-omics, Lambert et al. reflect on the key concepts underlying microfluidics and how resulting engineering advances at the microscale drove the evolution of genomic sequencing.