The potato (Solanum tuberosum) is the fourth most cultivated and consumed crop worldwide. The swelled stolonic region of the plant is economically important due to its considerable quantities of carbohydrates plus modest quantities of minerals and vitamins. Tuber formation is governed by various external and internal factors including light, oxygen concentration, photosynthate availability, phytochromes, transcription factors, and metabolite availability. This review updates and expands upon our current knowledge regarding the involvement of these variables in the tuberization process. Tuber formation starts at the onset of the supportive season under optimal light conditions where phytochromes in leaves sense the signal. The transmittance of the signal results in photosynthate accumulation, phloem loading with sucrose, phloem transport and unloading at the stolonic region, sucrose entry into the tuber cell, and conversion of sucrose to starch, all under the direction of regulatory enzymes. Several genes are associated with tuberization and regulated either positively or negatively. During the course of these cellular micro-reactions, a very fine stolonic tip will ultimately be transformed into a fully matured potato tuber. Tuber formation can be increased by genetic modifications, that further improve tuber yield and quality.