Electrospinning (E-spinning) is a process capable of fabricating nonwoven webs and well-aligned arrays of continuous nanofibers with controlled morphology, size, and structure from polymer solutions or melts in high-voltage electrostatic field. This chapter discusses the advances in the scale-up of nanofiber production by E-spinning, with primary focus on multi-needle and needleless E-spinning. Most investigations on multi-needle E-spinning have been focused on processes with two-dimensional needle arrays. Multi-needle spinning heads with elliptic and circular arrangements were designed to improve the process stability and also the production efficiency. The traditional “needle-type” E-spinning method is, in principle, subject to problems related to polymer clogging at the spinneret nozzle, which may limit the achievable throughput of continuous production processes. In order to reduce solution droplet from the electrodes onto the collector, upward needleless E-spinning is often used. In 2007, a new bottom-up gas-jet E-spinning process for mass production was presented by Y. Liu and J. H. He., which was also called “bubble E-spinning”.